J Alzheimers Dis Parkinsonism
· 2017 · PMID 29456879
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OBJECTIVE: Parkinson's disease (PD), caused by basal ganglia dysfunction, is associated with motor disturbances including dysarthria. Stimulation of the subthalamic nucleus, a preferred treatment targeting basal ganglia...OBJECTIVE: Parkinson's disease (PD), caused by basal ganglia dysfunction, is associated with motor disturbances including dysarthria. Stimulation of the subthalamic nucleus, a preferred treatment targeting basal ganglia function, improves features of the motor disorder, but has uncertain effects on speech.We studied speech during contrasting stimulation states to reveal subcortical effects on voice and articulation. Measures were made on selected samples of spontaneous and repeated speech. METHODS: Persons with Parkinson's disease (PWP) who had undergone bilateral deep brain stimulation of the subthalamic nucleus (DBS-STN) provided spontaneous speech samples and then repeated portions of their monologue both on and off stimulation. Excerpts were presented in a listening protocol probing intelligibility. Also analysed were a continuous phrase repetition task and a second spontaneous speech sample. Fundamental frequency (F0), harmonic-to-noise ratio (HNR), jitter, shimmer and fluency were measured in these three speech samples performed with DBS stimulation on and off. RESULTS: During subcortical stimulation, spontaneous excerpts were less intelligible than repeated excerpts. F0 and HNR were higher and shimmer was decreased in repetition and stimulation. Articulatory dysfluencies were increased for spontaneous speech and during stimulation in all three speech samples. CONCLUSION: Deep brain stimulation disrupts fluency and improves voice in spontaneous speech, reflecting an inverse influence of subcortical systems on articulatory posturing and laryngeal mechanisms. Better voice and less dysfluency in repetition may occur because an external model reduces the speech planning burden, as seen for gait and arm reach. These orthogonal results for fluency versus phonatory competence may account for ambivalent reports from dysarthric speakers and reveal the complexity of subcortical control of motor speech.
Malek-Ahmadi M, Lu S, Chan Y
… +3 more, Perez SE, Chen K, Mufson EJ
J Alzheimers Dis Parkinsonism
· 2017 · PMID 29423338
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OBJECTIVE: Years of education are the most common proxy for measuring cognitive reserve (CR) when assessing the relationship between Alzheimer's disease (AD) neuropathology and cognition. However, years of education may...OBJECTIVE: Years of education are the most common proxy for measuring cognitive reserve (CR) when assessing the relationship between Alzheimer's disease (AD) neuropathology and cognition. However, years of education may be limited as a CR proxy given that it represents a specific timeframe in early life and is static. Studies suggest that measures of intellectual function provide a dynamic estimate of CR that is superior to years of education since it captures the effect of continued learning over time. The present study determined whether dynamic measures of CR were better predictors of episodic memory and executive function in the presence of AD pathology than a static measure of CR. METHODS: Subjects examined died with a pre-mortem clinical diagnosis of no cognitive impaired, mild cognitive impairment and mild to moderate AD. CERAD and Braak stage were used to stratify the sample by AD pathology severity. Linear regression analyses using CR by CERAD and CR by Braak stage interaction terms were used to determine whether Extended Range Vocabulary Test (ERVT) scores or years of education were significantly associated with episodic memory composite (EMC) and executive function composite (EFC) performance. All models were adjusted for clinical diagnosis, age at death, gender, APOE e4 carrier status and Braak stage. RESULTS: For episodic memory, years of education by CERAD interaction were not statistically significant (β=-0.01, SE=0.01, p=0.53). By contrast, ERVT interaction with CERAD diagnosis was statistically significant (β=-0.03, SE=0.01, p=0.004). Among the models using Braak stages, none of the CR by pathology interactions were associated with EMC or EFC. CONCLUSION: Results suggest that a dynamic rather than a static measure is a better indicator of CR and that the relationship between CR and cognition is dependent upon the severity of select AD criteria.
J Alzheimers Dis Parkinsonism
· 2017 · PMID 29354323
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A number of experimental investigations utilizing different murine species have previously reported: (i) that standard mouse-diets supplemented with physiologically realistic amounts of neurotoxic metal salts substantial...A number of experimental investigations utilizing different murine species have previously reported: (i) that standard mouse-diets supplemented with physiologically realistic amounts of neurotoxic metal salts substantially induce pro-inflammatory signaling in a number of murine tissues; (ii) that these diet-stimulated changes may contribute to a systemic inflammation (SI), a potential precursor to neurodegenerative events in both the central and the peripheral nervous system (CNS, PNS); and (iii) that these events may ultimately contribute to a chronic and progressive inflammatory neurodegeneration, such as that which is observed in Alzheimer's disease (AD) brain. In these experiments we assayed for markers of SI in the blood serum of C57BL/6J mice after 0, 1, 3 and 5 months of exposure to a standard mouse diet that included aluminum-sulfate in the food and drinking water, compared to age-matched controls receiving magnesium-sulfate or no additions. The data indicate that the SI markers that include the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), the acute phase reactive protein C-reactive protein (CRP) production and a triad of pro-inflammatory microRNAs (miRNA-9, miRNA-125b and miRNA-146a) all increase in the serum after aluminum-sulfate exposure. For the first time these results suggest that exposure to aluminum-sulfate at physiologically realistic concentrations, as would be found in the human diet over the long term, may predispose to SI and the potential development of chronic, progressive, inflammatory neurodegeneration with downstream pathogenic consequences.
J Alzheimers Dis Parkinsonism
· 2017 Aug · PMID 29214114
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Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia among aged people whose population is rapidly increasing. AD not only seriously affects the patient's physical he...Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia among aged people whose population is rapidly increasing. AD not only seriously affects the patient's physical health and quality of life, but also adds a heavy burden to the patient's family and society. It is urgent to understand AD pathogenesis and develop the means of prevention and treatment. AD is a chronic devastating neurodegenerative disease without effective treatment. Current approaches for management focus on helping patients relieve or delay the symptoms of cognitive dysfunction. The calcium ion (Ca) is an important second messenger in the function and structure of nerve cell circuits in the brain such as neuronal growth, exocytosis, as well as in synaptic and cognitive function. Increasing numbers of studies suggested that disruption of intracellular Ca homeostasis, especially the abnormal and excessive Ca release from the endoplasmic reticulum (ER) via the ryanodine receptor (RYR), plays important roles in orchestrating the dynamic of the neuropathology of AD and associated memory loss, cognitive dysfunction. Dantrolene, a known antagonist of the RYR and a clinically available drug to treat malignant hyperthermia, can ameliorate the abnormal Ca+ release from the RYR in AD and the subsequent pathogenesis, such as increased β-secretase and γ-secretase activities, production of Amyloid-β 42 (Aβ 42) and its oligomer, impaired autophagy, synapse dysfunction, and memory loss. However, more studies are needed to confirm the efficacy and safety repurposing dantrolene as a therapeutic drug in AD.
Cukier HN, Kunkle BK, Hamilton KL
… +13 more, Rolati S, Kohli MA, Whitehead PL, Jaworski J, Vance JM, Cuccaro ML, Carney RM, Gilbert JR, Farrer LA, Martin ER, Beecham GW, Haines JL, Pericak-Vance MA
J Alzheimers Dis Parkinsonism
· 2017 Aug · PMID 29177109
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OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder for which more than 20 genetic loci have been implicated to date. However, studies demonstrate not all genetic factors have been identified. Therefore,...OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder for which more than 20 genetic loci have been implicated to date. However, studies demonstrate not all genetic factors have been identified. Therefore, in this study we seek to identify additional rare variants and novel genes potentially contributing to AD. METHODS: Whole exome sequencing was performed on 23 multi-generational families with an average of eight affected subjects. Exome sequencing was filtered for rare, nonsynonymous and loss-of-function variants. Alterations predicted to have a functional consequence and located within either a previously reported AD gene, a linkage peak (LOD>2), or clustering in the same gene across multiple families, were prioritized. RESULTS: Rare variants were found in known AD risk genes including and . Three families had five variants of interest in linkage regions with LOD>2. Genes with segregating alterations in these peaks include and , two genes that have both been implicated in immunity, , which encodes a catenin in the cerebral cortex and , a gene that may induce mitochondrial dysfunction and has the potential to damage neurons. Four genes were identified with alterations in more than one family include , a gene that causes Charcot-Marie-Tooth disease and , which promotes synaptogenesis. CONCLUSION: Utilizing large families with a heavy burden of disease allowed for the identification of rare variants co-segregating with disease. Variants were identified in both known AD risk genes and in novel genes.
J Alzheimers Dis Parkinsonism
· 2017 Apr · PMID 29051843
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RNA sequencing, DNA microfluidic array, LED-Northern, Western immunoassay and bioinformatics analysis have uncovered a small family of up-regulated human brain enriched microRNAs (miRNAs) and down-regulated messenger RNA...RNA sequencing, DNA microfluidic array, LED-Northern, Western immunoassay and bioinformatics analysis have uncovered a small family of up-regulated human brain enriched microRNAs (miRNAs) and down-regulated messenger RNAs (mRNAs) in short post-mortem interval (PMI) sporadic Alzheimer's disease (AD) brain. At the mRNA level, a large majority of the expression of human brain genes found to be down-regulated in sporadic AD appears to be a consequence of an up-regulation of a specific group of NF-kB-inducible microRNAs (miRNAs). This group of up-regulated miRNAs - including miRNA-34a and miRNA-146a - has strong, energetically favorable, complimentary RNA sequences in the 3' untranslated regions (3'-UTR) of their target mRNAs which ultimately drive the down-regulation in the expression of certain essential brain genes. Interestingly, just 2 significantly up-regulated miRNAs - miRNA-34a and miRNA-146a - appear to down-regulate mRNA targets involved in synaptogenesis (SHANK3), phagocytosis deficits and tau pathology (TREM2), inflammation (CFH; complement factor H) and amyloidogenesis (TSPAN12), all of which are distinguishing pathological features characteristic of middle-to-late stage AD neuropathology. This paper reports the novel finding of parallel miRNA-34a and miRNA-146a up-regulation in sporadic AD hippocampal CA1 RNA pools and proposes an altered miRNA-mRNA coupled signaling network in AD, much of which is supported by current experimental findings in the recent literature.
J Alzheimers Dis Parkinsonism
· 2017 Jun · PMID 28944096
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The thalamus is a critical module in the circuit which has been associated with movement disorders including dystonia. This circuit extends from cortex to striatum to pallidum to the thalamic nucleus Ventral Lateral ante...The thalamus is a critical module in the circuit which has been associated with movement disorders including dystonia. This circuit extends from cortex to striatum to pallidum to the thalamic nucleus Ventral Lateral anterior (VLa) to cortex and can be studied by activity recorded during thalamic stereotactic surgery for the treatment of dystonia. Neuronal recordings in the VLa nucleus show low frequency modulation of firing that is correlated with and leads the low frequency modulation of EMG activity; this EMG activity is characteristic of dystonia. Immediately posterior is the Ventral Lateral posterior (VLp) nucleus which, in controls (patients with tremor or chronic pain), is characterized by deep sensory cells which fire at short latency in response to movement of a single joint or to stimulation of deep structures, such as muscles, tendons and joints. In patients with dystonia, neurons with this sensory activity are much more common than in controls and single neurons often respond to movement of multiple joints. In controls operated for the treatment of tremor or chronic pain many neurons in both nuclei are activated during active or involuntary joint movements, such as tremor or dystonia. The active joint movement related to the firing of a cell is usually in the opposite direction to the passive joint movement which causes that cell to fire. This linkage of active or involuntary and passive joint movement is unfocussed in dystonia. The involuntary dystonic joint movement best correlated with firing of a neuron may not activate the neuron when it occurs as a passive movement, while multiple other passive movements will activate the neuron. These linkages may explain the overflow of isolated voluntary activity to multiple other muscles that is seen in dystonia. The activity of either nucleus may have a critical role in dystonia since their disruption by stimulation or lesioning can decrease dystonia.
Farran CJ, Etkin CD, Eisenstein A
… +7 more, Paun O, Rajan KB, Sweet CMC, McCann JJ, Barnes LL, Shah RC, Evans DA
J Alzheimers Dis Parkinsonism
· 2016 Aug · PMID 28752016
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OBJECTIVE: Alzheimer's disease and related dementias (ADRD) affect more than five million Americans and their family caregivers. Caregiving creates challenges, may contribute to decreased caregiver health and is associat...OBJECTIVE: Alzheimer's disease and related dementias (ADRD) affect more than five million Americans and their family caregivers. Caregiving creates challenges, may contribute to decreased caregiver health and is associated with $9.7 billion of caregiver health care costs. The purpose of this 12 month randomized clinical trial (RCT) was to examine if the Enhancing Physical Activity Intervention (EPAI), a moderate to vigorous physical activity (MVPA) treatment group, versus the Caregiver Skill Building Intervention (CSBI) control, would have greater: (1) MVPA adherence; and (2) physical function. METHODS: Caregivers were randomly assigned to EPAI or CSBI (N=211). MVPA was assessed using a self-report measure; and physical function was objectively assessed using two measures. Intention-to-treat analyses used descriptive, categorical and generalized estimating equations (GEE), with an exchangeable working correlation matrix and a log link, to examine main effects and interactions in change of MVPA and physical function over time. RESULTS: At 12 months, EPAI significantly increased MVPA (=<0.001) and number of steps (=< .01); maintained stable caregiving hours and use of formal services; while CSBI increased hours of caregiving (=<0.001) and used more formal services (=<0.02). Qualitative physical function data indicated that approximately 50% of caregivers had difficulties completing physical function tests. CONCLUSION: The EPAI had a stronger 12 month effect on caregiver MVPA and physical function, as well as maintaining stability of caregiving hours and formal service use; while CSBI increased caregiving hours and use of formal services. A study limitation included greater EPAI versus CSBI attrition. Future directions are proposed for dementia family caregiver physical activity research.
Shultz JM, Resnikoff H, Bondarenko V
… +4 more, Joers V, Mejia A, Simmons H, Emborg ME
J Alzheimers Dis Parkinsonism
· 2016 Nov · PMID 28090391
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OBJECTIVE: Constipation is a common non-motor symptom of Parkinson's disease (PD). Although pathology of the enteric nervous system (ENS) has been associated with constipation in PD, the contribution of catecholaminergic...OBJECTIVE: Constipation is a common non-motor symptom of Parkinson's disease (PD). Although pathology of the enteric nervous system (ENS) has been associated with constipation in PD, the contribution of catecholaminergic neurodegeneration to this symptom is currently debated. The goal of this study was to assess the effects of the neurotoxin 6-hydroxydopamine (6-OHDA) on the colonic myenteric plexus and shed light on the role of catecholaminergic innervation in gastrointestinal (GI) function. METHODS: Proximal colon tissue from 6-OHDA-treated (n=5) and age-matched control (n=5) rhesus monkeys was immunostained and quantified using ImageJ software. All animals underwent routine daily feces monitoring to assess for constipation or other GI dysfunction. RESULTS: Quantification of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)-immunoreactivity (-ir) revealed significant reduction in myenteric ganglia of 6-OHDA-treated animals compared to controls (TH-ir: 87.8%, <0.0001; AADC-ir: 61.7% =0.0034). Analysis of pan-neuronal markers (PGP9.5, HuC/D), other neurochemical phenotypes (VIP, nNOS), PD-associated pathology proteins (α-synuclein, phosphorylated α-synuclein), glial marker GFAP and neuroinflammation and oxidative stress (HLA-DR, CD45, Nitrotyrosine) did not show significant differences. Monitoring of feces revealed frequent (>30% days) soft stool or diarrhea in 2 of the 5 6-OHDA-treated animals and 0 of the 5 control animals during the 2 months prior to necropsy, with no animals exhibiting signs of constipation. CONCLUSION: Systemic administration of 6-OHDA to rhesus monkeys significantly reduced catecholaminergic expression in the colonic myenteric plexus without inducing constipation. These findings support the concept that ENS catecholaminergic loss is not responsible for constipation in PD.
J Alzheimers Dis Parkinsonism
· 2016 Nov · PMID 28042517
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Cerebral microbleeds (MB) and small vessel disease (SVD) with congophilic arterial angiopathy (CAA) are increasingly recognized as a variable factor in AD cognitive impairments. This commentary on our recent report on se...Cerebral microbleeds (MB) and small vessel disease (SVD) with congophilic arterial angiopathy (CAA) are increasingly recognized as a variable factor in AD cognitive impairments. This commentary on our recent report on sex-ApoE interactions in MBs published this February, briefly explores three aspects of MBs that could not be fully discussed therein: I, A possible gap between the prevalence of MBs as detected by MRI and post mortem analysis; II, The role of hemoglobin-degradation products in amyloid-attributed neurodegenerative changes; and III, Possible assessment of MB by cerebrospinal fluid (CSF) assays for iron-related markers to better screen patient subgroups for AD interventions.
J Alzheimers Dis Parkinsonism
· 2016 Oct · PMID 27882265
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Since the creation of induced Pluripotent Stem Cells (iPSCs) ten years ago, hundreds of publications have demonstrated their considerable impact on disease modeling and therapy. In this commentary, we will summarize key...Since the creation of induced Pluripotent Stem Cells (iPSCs) ten years ago, hundreds of publications have demonstrated their considerable impact on disease modeling and therapy. In this commentary, we will summarize key milestones, benefits and challenges in the iPSC field. Furthermore, we will highlight blood as an effective and easily accessible source for patient-specific iPSCs derivation in the context of work done in our laboratory and others.
Tong M, Dominguez C, Didsbury J
… +1 more, de la Monte SM
J Alzheimers Dis Parkinsonism
· 2016 Jun · PMID 27525190
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BACKGROUND: Alzheimer's disease (AD) could be regarded as a brain form of diabetes since insulin resistance and deficiency develop early and progress with severity of neurodegeneration. Preserving insulin's actions in th...BACKGROUND: Alzheimer's disease (AD) could be regarded as a brain form of diabetes since insulin resistance and deficiency develop early and progress with severity of neurodegeneration. Preserving insulin's actions in the brain restores function and reduces neurodegeneration. T3D-959 is a dual nuclear receptor agonist currently in a Phase 2a trial in mild-to-moderate AD patients (ClinicalTrials.gov identifier NCT02560753). Herein, we show that T3D-959 improves motor function and reverses neurodegeneration in a sporadic model of AD. METHODS: Long Evans rats were administered intracerebral (i.c.) streptozotocin (STZ) or normal saline (control) and dosed orally with T3D-959 (1.0 mg/kg/day) or saline for 21 or 28 days. Rotarod tests evaluated motor function. Histopathology with image analysis was used to assess neurodegeneration. RESULTS: T3D-959 significantly improved motor performance, and preserved both cortical and normalized white matter structure in i.c STZ-treated rats. T3D-959 treatments were effective when dosed therapeutically, whether initiated 1 day or 7 days after i.c. STZ. CONCLUSION: T3D-959's targeting neuro-metabolic dysfunctions via agonism of PPAR delta and PPAR gamma nuclear receptors provides potential disease modification in AD.
J Alzheimers Dis Parkinsonism
· 2015 Mar · PMID 25977840
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Since the inception of the human microbiome project (HMP) by the US National Institutes of Health (NIH) in 2007 there has been a keen resurgence in our recognition of the human microbiome and its contribution to developm...Since the inception of the human microbiome project (HMP) by the US National Institutes of Health (NIH) in 2007 there has been a keen resurgence in our recognition of the human microbiome and its contribution to development, immunity, neurophysiology, metabolic and nutritive support to central nervous system (CNS) health and disease. What is not generally appreciated is that (i) the ~10 microbial cells that comprise the human microbiome outnumber human host cells by approximately one hundred-to-one; (ii) together the microbial genes of the microbiome outnumber human host genes by about one hundred-and-fifty to one; (iii) collectively these microbes constitute the largest 'diffuse organ system' in the human body, more metabolically active than the liver; strongly influencing host nutritive-, innate-immune, neuroinflammatory-, neuromodulatory- and neurotransmission-functions; and (iv) that these microbes actively secrete highly complex, immunogenic mixtures of lipopolysaccharide (LPS) and amyloid from their outer membranes into their immediate environment. While secreted LPS and amyloids are generally quite soluble as monomers over time they form into highly insoluble fibrous protein aggregates that are implicated in the progressive degenerative neuropathology of several common, age-related disorders of the human CNS including Alzheimer's disease (AD). This general commentary-perspective paper will highlight some recent findings on microbial-derived secreted LPS and amyloids and the potential contribution of these neurotoxic and proinflammatory microbial exudates to age-related inflammatory amyloidogenesis and neurodegeneration, with specific reference to AD wherever possible.
Tsai A, Malek-Ahmadi M, Kahlon V
… +1 more, Sabbagh MN
J Alzheimers Dis Parkinsonism
· 2014 May · PMID 25937995
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OBJECTIVE: In the present study, cerebrospinal fluid (CSF) profiles were assessed to determine how idiopathic normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) differs. METHODS: Subjects were drawn from pa...OBJECTIVE: In the present study, cerebrospinal fluid (CSF) profiles were assessed to determine how idiopathic normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) differs. METHODS: Subjects were drawn from patients who underwent lumbar punctures as part of their diagnostic evaluations in the Banner Sun Health Research Institute Memory Disorders clinic. The clinical sample included 11 iNPH subjects (mean age 81.36±2.58) and 11 AD subjects (mean age 61.46±8.24). Concentrations of amyloid-β (Aβ42), total-tau (t-tau), phospho-tau181 (p-tau) Aβ42, and an Aβ42-Tau Index (ATI) were measured by commercial assay (Athena Diagnostics). and compared to each other. The Mann-Whitney test was used to assess group differences on the raw values for Aβ42, t-tau, p-tau, ATI, age, education, and MMSE. RESULTS: In a univariate analysis, p-tau was found to be significantly (P = 0.009) lower in patients diagnosed with iNPH than those with AD. Amyloid-β (Aβ42), total-tau (t-tau) did not differ between groups. In multi-variate analysis, the differences in p-tau between groups did not differ. CONCLUSION: Although age could represent a significant confound, p-tau is significantly lower in iNPH compared to AD. P-tau would be expected to increase with age but in this sample is lower suggesting the difference might be explained by the underlying condition.
Yaghmoor F, Noorsaeed A, Alsaggaf S
… +4 more, Aljohani W, Scholtzova H, Boutajangout A, Wisniewski T
J Alzheimers Dis Parkinsonism
· 2014 Nov · PMID 25664220
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Alzheimer's disease (AD) is the leading cause of dementia worldwide. Late-onset AD (LOAD), is the most common form of Alzheimer's disease, representing about >95% of cases and early-onset AD represents <5% of cases. Seve...Alzheimer's disease (AD) is the leading cause of dementia worldwide. Late-onset AD (LOAD), is the most common form of Alzheimer's disease, representing about >95% of cases and early-onset AD represents <5% of cases. Several risk factors have been discovered that are associated with AD, with advancing age being the most prominent. Other environmental risk factors include diabetes mellitus, level of physical activity, educational status, hypertension and head injury. The most well known genetic risk factor for LOAD is inheritance of the apolipoprotein (apo) E4 allele. Recently, rare variants of TREM2 have been reported as a significant risk factor for LOAD, comparable to inheritance of apoE4. In this review we will focus on the role(s) of TREM2 in AD as well as in other neurodegenerative disorders.
J Alzheimers Dis Parkinsonism
· 2014 Apr · PMID 25343059
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Current Positron Emission Tomography (PET) biomarkers for Alzheimer's disease (AD) assess either neuronal function, or associated pathological features of this common neurodegenerative disease. The most widely accepted c...Current Positron Emission Tomography (PET) biomarkers for Alzheimer's disease (AD) assess either neuronal function, or associated pathological features of this common neurodegenerative disease. The most widely accepted clinical PET tool for AD is 18-fluorodeoxyglucose PET (FDG-PET), which measures cerebral metabolic glucose utilization rate (CMRglc). FDG-PET is a marker of synaptic activity, neuronal function, and neuronal metabolic activity. AD is characterized by a distinct pattern of hypometabolism, as seen with the FDG images. This pattern can show variability across different subjects and is present before a patient is demented, specifically in amnestic mild cognitive impairment a clinical diagnosis defined as an intermediate state from normal aging to dementia. In addition to FDG PET, novel PET approaches assess known pathological hallmarks of AD including extracellular amyloid-beta plaques (Aβ) and intracellular neurofibrillary tangles composed of tau fibrils. Already, amyloid PET imaging is a tool that allows imaging of extracellular beta-amyloid levels. Efforts to bring tau imaging into clinical use continue, but this approach is hampered by the intracellular nature of tau protein deposition, subsequent weak radiotracer binding, and low image contrast. Several new candidate probes for tau-specific PET imaging are currently available but have not found their way into broad clinical applications. This study gives an overview of the most recent PET-based neuroimaging techniques for AD. We place special emphasis on PET data analysis and interpretation techniques, as well as radiochemistry for imaging metabolism and assessing Aβ and tau pathology.
J Alzheimers Dis Parkinsonism
· 2014 Jan · PMID 25324979
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Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbid...Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.