TY - JOUR
T1 - The complex pathway between amyloid β and cognition
T2 - implications for therapy
AU - Jagust, William J.
AU - Teunissen, Charlotte E.
AU - DeCarli, Charles
N1 - Funding Information: This Personal View was supported, in part, by NIH grants to WJJ (numbers AG034570 and AG062542), WJJ and CD (number AG024904), and CD (numbers AG072972, NS120384, and AG075758). The funders had no involvement in the preparation of the Personal View. The authors thank Susan Landau for critical comments on an earlier version of the Personal View. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/9/1
Y1 - 2023/9/1
N2 - For decades, the hypothesis that brain deposition of the amyloid β protein initiates Alzheimer's disease has dominated research and clinical trials. Targeting amyloid β is starting to produce therapeutic benefit, although whether amyloid-lowering drugs will be widely and meaningfully effective is still unclear. Despite extensive in-vivo biomarker evidence in humans showing the importance of an amyloid cascade that drives cognitive decline, the amyloid hypothesis does not fully account for the complexity of late-life cognitive impairment. Multiple brain pathological changes, inflammation, and host factors of resilience might also be involved in contributing to the development of dementia. This variability suggests that the benefits of lowering amyloid β might depend on how strongly an amyloid pathway is manifest in an individual in relation to other coexisting pathophysiological processes. A new approach to research and treatment, which fully considers the multiple factors that drive cognitive decline, is necessary.
AB - For decades, the hypothesis that brain deposition of the amyloid β protein initiates Alzheimer's disease has dominated research and clinical trials. Targeting amyloid β is starting to produce therapeutic benefit, although whether amyloid-lowering drugs will be widely and meaningfully effective is still unclear. Despite extensive in-vivo biomarker evidence in humans showing the importance of an amyloid cascade that drives cognitive decline, the amyloid hypothesis does not fully account for the complexity of late-life cognitive impairment. Multiple brain pathological changes, inflammation, and host factors of resilience might also be involved in contributing to the development of dementia. This variability suggests that the benefits of lowering amyloid β might depend on how strongly an amyloid pathway is manifest in an individual in relation to other coexisting pathophysiological processes. A new approach to research and treatment, which fully considers the multiple factors that drive cognitive decline, is necessary.
UR - http://www.scopus.com/inward/record.url?scp=85167980721&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S1474-4422(23)00128-X
DO - https://doi.org/10.1016/S1474-4422(23)00128-X
M3 - Review article
C2 - 37454670
SN - 1474-4422
VL - 22
SP - 847
EP - 857
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 9
ER -