Alzheimer’s disease: challenging the amyloid dogma
The predominant hypothesis for the pathogenesis of Alzheimer’s disease suggests that the deposition of fibrillar amyloid in the brain is its causative trigger. However, the repeated failures of Alzheimer’s diseases treatment trials targeting amyloid deposition or clearance have highlighted the need to enhance understanding of alternative disease mechanisms.
IRP researchers led by Madhav Thambisetty, M.D., Ph.D., discovered that a common genetic risk variant for Alzheimer’s disease in the complement receptor-1 (CR1) gene is associated with lower brain amyloid burden in at-risk older individuals.
This study is the first demonstration that a genetic risk factor may mediate Alzheimer’s disease pathogenesis by mechanisms distinct from increased deposition of fibrillar amyloid in the brain. The team's findings have highlighted the importance of seeking alternative mechanisms underlying Alzheimer's disease and renew hope that identification of such mechanisms may lead to effective treatments.
Thambisetty M, An Y, Nalls M, Sojkova J, Swaminathan S, Zhou Y, Singleton AB, Wong DF, Ferrucci L, Saykin AJ, Resnick SM. (2013). The Effect of CR1 on Brain Amyloid Burden during Aging and its Modification by APOE Genotype. Biological Psychiatry. 73(5), 422-8.
Gandy S, Haroutunian V, DeKosky ST, Sano M, Schadt EE. (2013). CR1 and the “vanishing amyloid” hypothesis of Alzheimer's disease. Biological Psychiatry. 73(5), 393‐5.
This page was last updated on Friday, January 14, 2022