From patients to disease: the difficult case of Alzheimer's

In individuals with sporadic Alzheimer's disease, amyloid β deposition might be driven by a different mechanism to that seen in people with autosomal dominant disease (eg, decreased clearance of amyloid β instead of overproduction) and by a stronger role of stochastic influences (eg, risk-modif...

Full description

Saved in:
Bibliographic Details
Published in:Lancet neurology 2022-02, Vol.21 (2), p.105-106
Main Authors: Frisoni, Giovanni B, Lathuilière, Aurelien
Format: Article
Language:English
Subjects:
Alzheimer's disease
Apolipoprotein E
Biomarkers
Cerebrospinal fluid
Coexistence
Cognitive ability
Dementia
Dementia disorders
FDA approval
Genetic diversity
Hypotheses
Mutation
Neocortex
Neurodegenerative diseases
Stochasticity
Tau protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In individuals with sporadic Alzheimer's disease, amyloid β deposition might be driven by a different mechanism to that seen in people with autosomal dominant disease (eg, decreased clearance of amyloid β instead of overproduction) and by a stronger role of stochastic influences (eg, risk-modifying genetic variants, environmental exposures, and cognitive reserve). [...]it is perhaps unsurprising that drugs developed with treatment of autosomal dominant Alzheimer's disease in mind have disappointing efficacy in individuals with the more complex sporadic form of disease. The drivers of tau pathological progression seem to differ after entering the clinical phase of Alzheimer's disease and could be related to the coexistence of amyloid β and tau pathologies in the neocortex.5 Inclusion of tau-related biomarkers (eg, PET, CSF, or blood measurements) in biomarker trajectory models developed by Chhatwal and colleagues could improve our understanding of synergies between amyloid β and tau, and their contribution to clinical disease. Three variants of Alzheimer's disease—autosomal dominant Alzheimer's disease, APOE ɛ4-related sporadic Alzheimer's disease, and APOE ɛ4-unrelated sporadic Alzheimer's disease—feature decreasing penetrance of the amyloid pathophysiological cascade and the consequent lifetime risk of Alzheimer's disease dementia (almost 100%, 22–95%, and 7–35%, respectively). [...]stochastic factors (ie, environmental exposures and lower-risk genes, such as TREM2, ABCA7, PLCG2, CLU, CR1, and CD33) carried increasing weight.
ISSN:1474-4422
1474-4465
DOI:10.1016/S1474-4422(21)00461-0