scholarly journals Amyloid-beta and phosphorylated tau in post-mortem Alzheimer’s disease retinas

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Jurre den Haan ◽  
Tjado H. J. Morrema ◽  
Frank D. Verbraak ◽  
Johannes F. de Boer ◽  
Philip Scheltens ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Phosphorylated Tau ◽  
Post Mortem

scholarly journals Amyloid-beta, p-tau, and reactive microglia load are correlates of MRI cortical atrophy in Alzheimer's disease

2021 ◽  
Author(s):  
Irene Frigerio ◽  
Baayla DC Boon ◽  
Chen-Pei Lin ◽  
Yvon Galis-de Graaf ◽  
John GJM Bol ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cortical Thickness ◽  
Amyloid Beta ◽  
Brain Regions ◽  
Cortical Atrophy ◽  
Strongly Correlated ◽  
Phosphorylated Tau ◽  
Post Mortem ◽  
Reactive Microglia

INTRODUCTION: The aim of this study was to identify the histopathological correlates of MRI cortical atrophy in (a)typical Alzheimer's disease (AD) donors. METHODS: 19 AD and 10 control donors underwent post-mortem in-situ 3T-3DT1-MRI, from which cortical thickness was calculated. Upon subsequent autopsy, 21 cortical brain regions were selected and immunostained for amyloid-beta, phosphorylated-tau, and reactive microglia. MRI-pathology associations were assessed using linear mixed models. Post-mortem MRI was compared to ante-mortem MRI when available. RESULTS: Higher amyloid-beta load weakly correlated with a higher cortical thickness globally. Phosphorylated-tau strongly correlated with cortical atrophy in temporo-frontal regions. Reactive microglia load strongly correlated with cortical atrophy in the parietal region. Post-mortem scans showed high concordance with ante-mortem scans acquired <1 year before death. DISCUSSION: Distinct histopathological markers differently correlate with cortical atrophy, highlighting their different roles in the neurodegenerative process. This study contributes in understanding the pathological underpinnings of MRI atrophy patterns.

scholarly journals Visit-to-visit Blood Pressure Variability and Regional Cerebral Perfusion Decline in Older Adults

2020 ◽  
Author(s):  
Isabel Sible ◽  
Belinda Yew ◽  
Shubir Dutt ◽  
Katherine J. Bangen ◽  
Yanrong Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Blood Pressure Variability ◽  
Cerebral Perfusion ◽  
Cerebral Spinal Fluid ◽  
Spinal Fluid ◽  
Phosphorylated Tau

Abstract Background: Blood pressure variability has been linked to dementia risk, independent of average blood pressure levels. It has been hypothesized that dysregulated blood pressure may challenge autoregulatory mechanisms and risk cerebral hypoperfusion. The current study examined whether visit-to-visit blood pressure variability over one year is related to concurrent regional cerebral perfusion decline over the same period in older adults.Methods: Sixty-three older adults without history of dementia or stroke underwent repeated blood pressure measurement and arterial spin-labelling magnetic resonance imaging over the same one year period. Fluorodeoxyglucose-positron emission tomography determined cerebral metabolism at baseline. A subset underwent lumbar puncture to detect cerebral spinal fluid amyloid-beta (n=18) and phosphorylated tau (n=21) abnormalities. Visit-to-visit blood pressure variability and change in regional cerebral perfusion were both calculated over 12 months. Multiple linear regression examined relationships between blood pressure variability and change in regional perfusion after controlling for age, sex, average blood pressure, antihypertensive medication use and cerebral metabolism. Exploratory analyses were repeated in participant subsets with abnormal cerebral spinal fluid amyloid-beta and phosphorylated tau.Results: Elevated blood pressure variability was related to perfusion decline in medial orbitofrontal cortex (ß = -.36; p = .008), hippocampus (ß = -.37; p = .005), entorhinal cortex (ß = -.48; p < .001), precuneus (ß = -.31; p = .02), inferior parietal cortex (ß = -.44; p < .001) and inferior temporal cortex (ß = -.46; p < .001). Elevated blood pressure variability was similarly related to perfusion decline in some regions among participant subsets showing abnormal cerebral spinal fluid amyloid-beta and phosphorylated tau.Conclusions: Older adults with elevated visit-to-visit blood pressure variability exhibit concurrent regional cerebral perfusion decline in areas vulnerable to cerebrovascular dysfunction in Alzheimer’s disease, independent of cerebral hypometabolism. Similar findings are observed in exploratory analyses of older adults with Alzheimer’s disease biomarker abnormalities. The study is limited by the small sample size, particularly the subset of participants with Alzheimer’s disease biomarker abnormalities. Findings may have therapeutic implications, given that certain antihypertensive medications have differential effects on variability of blood pressure independent of average levels.

scholarly journals Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

2021 ◽  
Author(s):  
Niall Murphy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Amyloid Beta ◽  
Memory Loss ◽  
Phosphorylated Tau ◽  
Disease Research ◽  
Neurodegenerative Process ◽  
The Relationship ◽  
The Brain

Alzheimer’s Disease is defined as progressive memory loss coincident with accumulation of aggregated amyloid beta and phosphorylated tau. Identifying the relationship between these features has guided Alzheimer’s Disease research for decades, principally with the view that aggregated proteins drive a neurodegenerative process. Here I propose that amyloid beta and phospho-tau write-protect and tag neuroplastic changes as they form, protecting and insuring established neuroplasticity from corruption. In way of illustration, binding of oligomeric amyloid beta to the prion receptor is presented as an example possible mechanism. The write-protecting process is conjected to occur at least partially under the governance of isodendritic neuromodulators such as norepinephrine and acetylcholine. Coincident with aging, animals are exposed to accumulating amounts of memorable information. Compounded with recent increases in life expectancy and exposure to information-rich environments this causes aggregating proteins to reach unforeseen toxic levels as mnemonic circuits overload. As the brain cannot purposefully delete memories nor protect against overaccumulation of aggregating proteins, the result is catastrophic breakdown on cellular and network levels causing memory loss.

scholarly journals Blood pressure variability and medial temporal atrophy in apolipoprotein ϵ4 carriers

2021 ◽  
Author(s):  
Isabel J. Sible ◽  
Daniel A. Nation ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Amyloid Beta ◽  
Blood Pressure Variability ◽  
Credible Interval ◽  
Carrier Status ◽  
Phosphorylated Tau ◽  
Disease Biomarker

AbstractBlood pressure variability is an emerging risk factor for dementia but relationships with markers of neurodegeneration and Alzheimer’s disease risk are understudied. We investigated blood pressure variability over one year and follow-up medial temporal brain volume change in apolipoprotein ϵ4 carriers and non-carriers, and in those with and without Alzheimer’s disease biomarker abnormality. 1051 Alzheimer’s Disease Neuroimaging Initiative participants without history of dementia or stroke underwent 3–4 blood pressure measurements over 12 months and ≥ 1 MRI thereafter. A subset (n = 252) underwent lumbar puncture to determine Alzheimer’s disease cerebral spinal fluid amyloid-beta and phosphorylated tau biomarker abnormality. Blood pressure variability over 12 months was calculated as variability independent of mean. Longitudinal hippocampal and entorhinal cortex volume data were extracted from serial brain MRI scans obtained after the final blood pressure measurement. Apolipoprotein ϵ4 carrier status was defined as at least one ϵ4 allele. Bayesian growth modelling revealed a significant interaction of blood pressure variability by ϵ4 by time on hippocampal (ß: -2.61 [95% credible interval -3.02, -2.12]) and entorhinal cortex (ß: -1.47 [95% credible interval -1.71, -1.17]) volume decline. A similar pattern emerged in subsets with Alzheimer’s disease pathophysiology (i.e., abnormal levels of both amyloid-beta and phosphorylated tau). Findings suggest that elevated blood pressure variability is related to medial temporal volume loss specifically in ϵ4 carriers, and in those with Alzheimer’s disease biomarker abnormality. Findings could implicate blood pressure variability in medial temporal neurodegeneration observed in older ϵ4 carriers and those with prodromal Alzheimer’s disease.

scholarly journals Assessment of cerebral microbleeds by susceptibility-weighted imaging in Alzheimer’s disease patients: A neuroimaging biomarker of the disease

2017 ◽  
Vol 30 (4) ◽  
pp. 330-335 ◽  
Author(s):  
Gianvincenzo Sparacia ◽  
Francesco Agnello ◽  
Giuseppe La Tona ◽  
Alberto Iaia ◽  
Federico Midiri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Amyloid Beta ◽  
Cerebral Microbleeds ◽  
Susceptibility Weighted Imaging ◽  
Phosphorylated Tau ◽  
Protein Levels ◽  
Phosphorylated Tau 181

Purpose The objective of this study was to correlate the presence and distribution of cerebral microbleeds in Alzheimer’s disease patients with cerebrospinal fluid biomarkers (amyloid-beta and phosphorylated tau 181 protein levels) and cognitive decline by using susceptibility-weighted imaging magnetic resonance sequences at 1.5 T. Material and methods Fifty-four consecutive Alzheimer’s disease patients underwent brain magnetic resonance imaging at 1.5 T to assess the presence and distribution of cerebral microbleeds on susceptibility-weighted imaging images. The images were analyzed in consensus by two neuroradiologists, each with at least 10 years’ experience. Dementia severity was assessed with the Mini-Mental State Examination score. A multiple regression analysis was performed to assess the associations between the number and location of cerebral microbleed lesions with the age, sex, duration of the disease, cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels, and cognitive functions. Results A total of 296 microbleeds were observed in 54 patients; 38 patients (70.4%) had lobar distribution, 13 patients (24.1%) had non-lobar distribution, and the remaining three patients (5.6%) had mixed distribution, demonstrating that Alzheimer’s disease patients present mainly a lobar distribution of cerebral microbleeds. The age and the duration of the disease were correlated with the number of lobar cerebral microbleeds ( P < 0.001). Cerebrospinal fluid amyloid-beta, phosphorylated tau 181 protein levels, and cognitive decline were correlated with the number of lobar cerebral microbleeds in Alzheimer’s disease patients ( P < 0.001). Conclusion Lobar distribution of cerebral microbleeds is associated with Alzheimer’s disease and the number of lobar cerebral microbleeds directly correlates with cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels and with the cognitive decline of Alzheimer’s disease patients.

scholarly journals Emergence of distinct and heterogeneous strains of amyloid beta with advanced Alzheimer’s disease pathology in Down syndrome

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alison M. Maxwell ◽  
Peng Yuan ◽  
Brianna M. Rivera ◽  
Wilder Schaaf ◽  
Mihovil Mladinov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Beta ◽  
Fluorescent Probes ◽  
Clinical Symptoms ◽  
Critical Role ◽  
Post Mortem ◽  
Post Mortem Brain ◽  
And Control

AbstractAmyloid beta (Aβ) is thought to play a critical role in the pathogenesis of Alzheimer’s disease (AD). Prion-like Aβ polymorphs, or “strains”, can have varying pathogenicity and may underlie the phenotypic heterogeneity of the disease. In order to develop effective AD therapies, it is critical to identify the strains of Aβ that might arise prior to the onset of clinical symptoms and understand how they may change with progressing disease. Down syndrome (DS), as the most common genetic cause of AD, presents promising opportunities to compare such features between early and advanced AD. In this work, we evaluate the neuropathology and Aβ strain profile in the post-mortem brain tissues of 210 DS, AD, and control individuals. We assayed the levels of various Aβ and tau species and used conformation-sensitive fluorescent probes to detect differences in Aβ strains among individuals and populations. We found that these cohorts have some common but also some distinct strains from one another, with the most heterogeneous populations of Aβ emerging in subjects with high levels of AD pathology. The emergence of distinct strains in DS at these later stages of disease suggests that the confluence of aging, pathology, and other DS-linked factors may favor conditions that generate strains that are unique from sporadic AD.

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