Support for the Amyloid Theory and Potential Preventative Treatment

The GliaCure team was excited by a recent study out of the University of Finland. Led by Mikko Hiltunen, the group provided support for the hypothesis that amyloid beta (Aβ) plays a key role in the pathology of Alzheimer’s disease. Five years ago an Icelandic team discovered that a mutation in the amyloid precursor protein (APP) protected carriers against Alzheimer’s disease, apparently by decreasing production of Aβ peptides. The Finnish study, published in the Annals of Neurology, indicates that Finnish men with the mutation known as A673T have on average 20% less plasma Aβ than those without the gene. While this study does not show a clear cause and effect, it does provide correlative evidence for the amyloid cascade theory, which had been called into question by clinical trial results reported by large pharma in the past few years.

Encouraging news also came out of a study published by Michael Donohue and Paul Aulsen of USC San Diego who based on a longitudinal data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The team measured brain amyloid in cognitively normal people at baseline, then tracked their cognitive performance and other measures for up to a decade, discovering that those who initially had elevated amyloid showed a clear decline in cognitive abilities while those with normal Aβ generally maintained their performance. Their study indicates that a therapy targeting amyloid deposition could be efficacious in preventing Alzheimer’s disease in those who have amyloid plaques in their brain but are not yet exhibiting cognitive decline.

Martiskainen H, Herukka SK, Stančáková A, Paananen J, Soininen H, Kuusisto J, Laakso M, Hiltunen M. Decreased plasma β-amyloid in the Alzheimer’s disease APP A673T variant carriers. Ann Neurol. 2017 May 26.

Donohue MC, Sperling RA, Petersen R, Sun CK, Weiner MW, Aisen PS, Alzheimer’s Disease Neuroimaging Initiative. Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons. JAMA. 2017 Jun 13;317(22):2305-2316.