scholarly journals The Neurochemistry of Alzheimer’s Disease: One of the Most Common Causes of Reduced Capability in the Adult Population

2022 ◽  
pp. 81-93
Author(s):  
Kaj Blennow ◽  
Henrik Zetterberg
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Susceptibility Gene ◽  
Tau Pathology ◽  
Blood Biomarkers ◽  
Neurofilament Light ◽  
Risk Profiling ◽  
Lifestyle Risk ◽  
Intervention Trials

AbstractAlzheimer’s disease (AD) is the most common form of dementia and is characterised by the triad of amyloid plaques, tau pathology and neurodegeneration. Except for a strong association with the susceptibility gene, specifically the apolipoprotein E (APOE) ε4 allele, the pathogenesis of the most common age-related sporadic form of AD is largely unknown. However, several genetic and environmental risk factors have been proposed. A potential problem is that most population-based studies on AD risk-profiling have not used biomarkers reflecting amyloid and tau pathology to classify patients and controls. Given the complex pathophysiology of late-onset AD and the difficulties in correctly diagnosing AD on purely clinical grounds, this introduces a risk of misclassification of both control subjects and clinically diagnosed AD cases. Importantly, in recent years, there has been a very successful development of blood biomarkers for AD pathophysiologies, including brain amyloidosis (amyloid β ratio), tau pathology (phosphorylated tau) and neurodegeneration (neurofilament light). Numerous studies have shown these biomarkers to correlate with amyloid and tau pathology load evaluated by PET and with MRI measures of neurodegeneration, and to predict future cognitive decline. The employment of blood biomarkers in epidemiological studies may foster an understanding of which and how specifically lifestyle risk factors are linked to AD, and repeated blood sampling in intervention trials may provide evidence as to whether controlling lifestyle factors may affect specific AD pathophysiologies.

scholarly journals Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease

Brain ◽  
2020 ◽  
Author(s):  
Joana B Pereira ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Hlin Kvartsberg ◽  
Ann Brinkmalm ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Light Chain ◽  
Diffusion Tensor ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Dependent Manner ◽  
Tau Pathology ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer’s disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor imaging. We found that the presynaptic and postsynaptic markers SNAP25, GAP43 and NRGN are elevated in early Alzheimer’s disease i.e. in amyloid-β-positive individuals without evidence of tau pathology. These markers were associated with greater amyloid-β pathology, worse memory and functional changes in the default mode network. In contrast, neurofilament light chain was abnormal in later disease stages, i.e. in individuals with both amyloid-β and tau pathology, and correlated with more tau and worse global cognition. Altogether, these findings support the hypothesis that amyloid-β and tau might have differential downstream effects on synaptic and axonal function in a stage-dependent manner, with amyloid-related synaptic changes occurring first, followed by tau-related axonal degeneration.

scholarly journals Research criteria for the diagnosis of Alzheimer's disease: genetic risk factors, blood biomarkers and olfactory dysfunction

2008 ◽  
Vol 20 (4) ◽  
pp. 853-855 ◽  
Author(s):  
Jonathan Foster ◽  
Hamid Sohrabi ◽  
Giuseppe Verdile ◽  
Ralph Martins
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Olfactory Dysfunction ◽  
Blood Biomarkers ◽  
Diagnostic Framework ◽  
Research Criteria

We note with interest the recently proposed new diagnostic framework published in Lancet Neurology entitled “Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria” by Dubois et al. (2007).

scholarly journals Alzheimer’s disease susceptibility gene apolipoprotein e (APOE) and blood biomarkers in UK Biobank (N=395,769)

2020 ◽  
Author(s):  
Amy C. Ferguson ◽  
Rachana Tank ◽  
Laura M. Lyall ◽  
Joey Ward ◽  
Carlos Celis-Morales ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Apolipoprotein E ◽  
Genetic Risk ◽  
Susceptibility Gene ◽  
Density Lipoprotein ◽  
European Ancestry ◽  
Uk Biobank ◽  
Blood Biomarkers

AbstractBackground and objectiveAlzheimer’s disease (AD) is a neurodegenerative condition where the underlying aetiology is still unclear. Investigating the potential influence of apolipoprotein e (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk. Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.MethodsAfter quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.ResultsSeveral biomarkers significantly associated with APOE e4 ‘risk’ and e2 ‘protective’ genotypes (vs. neutral e3/e3). Most associations supported previous data: for example, e4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p<0.001) and e2 with lower LDL (b = −0.456 SDs, p<0.001). There were however instances of associations found in unexpected directions: e.g. e4 and increased insulin-like growth factor (IGF-1) (standardized beta = 0.017, p<0.001) where lower levels have been previously suggested as an AD risk factor.ConclusionsThese findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence here in supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.

scholarly journals Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

2021 ◽  
Vol 10 (16) ◽  
pp. 3639
Author(s):  
Laia Montoliu-Gaya ◽  
Andre Strydom ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
Nicholas James Ashton
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Β ◽  
Detection Methods ◽  
Blood Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Positron Emission ◽  
Diagnosis Of Dementia

Epidemiological evidence suggests that by the age of 40 years, all individuals with Down syndrome (DS) have Alzheimer’s disease (AD) neuropathology. Clinical diagnosis of dementia by cognitive assessment is complex in these patients due to the pre-existing and varying intellectual disability, which may mask subtle declines in cognitive functioning. Cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, although accurate, are expensive, invasive, and particularly challenging in such a vulnerable population. The advances in ultra-sensitive detection methods have highlighted blood biomarkers as a valuable and realistic tool for AD diagnosis. Studies with DS patients have proven the potential blood-based biomarkers for sporadic AD (amyloid-β, tau, phosphorylated tau, and neurofilament light chain) to be useful in this population. In addition, biomarkers related to other pathologies that could aggravate dementia progression—such as inflammatory dysregulation, energetic imbalance, or oxidative stress—have been explored. This review serves to provide a brief overview of the main findings from the limited neuroimaging and CSF studies, outline the current state of blood biomarkers to diagnose AD in patients with DS, discuss possible past limitations of the research, and suggest considerations for developing and validating blood-based biomarkers in the future.

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