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Drugs that boost neurotrophic support might be helpful in early dementia

JAMA Neurology
Reuters Health - 31/01/2022 - A naturally occurring polymorphism in brain-derived neurotrophic factor may be an important moderator of cognitive impairment and levels of site-specific tau phosphorylation in dominantly inherited Alzheimer disease (DIAD), new research suggests. 

DIAD is a rare form of AD that causes memory loss and dementia in people typically in their 30s, 40s and 50s. 

In presymptomatic DIAD, polymorphism in the brain-derived neurotrophic factor (BDNF) gene resulting in a valine (Val) to methionine (Met) substitution at codon 66 (BDNF Val66Met) has been shown to moderate increases in cerebrospinal fluid levels of tau and phosphorylated tau 181 (p-tau181) and cognitive decline. 

Research has also shown that p-tau181 and p-tau217 in cerebrospinal fluid increase with initial beta-amyloid aggregation. 

For their study, published in JAMA Neurology, Dr. Yen Ying Lim with Monash University in Australia and colleagues asked the question: To what extent does the BDNF Val66Met polymorphism moderate cognitive performance and tau levels in DIAD? 

They analyzed data on 374 adults enrolled in the Dominantly Inherited Alzheimer Network (DIAN), including 144 mutation noncarriers, 156 presymptomatic mutation carriers and 74 symptomatic mutation carriers. For mutation carriers, only those with available BDNF Val66Met polymorphism data were included. 

In presymptomatic mutation carriers, compared with BDNF Val66 homozygotes, those who also had the BDNF Met66 allele showed significantly poorer episodic memory, smaller hippocampal volume, and higher p-tau217, p-tau181, and total tau, the researchers report. 

In symptomatic mutation carriers, compared with Val66 homozygotes, Met66 carriers showed significantly poorer global cognition and higher p-tau217, total tau, and p-tau205. 

"In DIAD, both clinical disease stage and the BDNF Met66 allele moderated the extent to which levels of site-specific tau phosphorylation were increased, hippocampal volume was decreased, and cognition impaired," the authors write in their paper. 

"These data reinforce earlier clinical and biomarker findings that BDNF Val66Met moderated the downstream association of beta-amyloid with AD clinical disease progression," they add. 

"This suggests that pharmacological strategies designed to increase neurotrophic support in the presymptomatic stages of AD may be beneficial," they conclude. 

SOURCE: https://bit.ly/3reeMXI JAMA Neurology, online January 31, 2022. 

By Reuters Staff 

© 2023 The Author(s). Published by Medicom Medical Publishers.
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