Presynaptic membrane protein dysfunction occurs prior to neurodegeneration and predicts faster cognitive decline

So you described a problem, DID NOTHING TO SOLVE IT! Useless.

Presynaptic membrane protein dysfunction occurs prior to neurodegeneration and predicts faster cognitive decline

Guoyu Lan, Anqi Li, Zhen Liu, Shaohua Ma, Tengfei Guo, for the Alzheimer's Disease Neuroimaging Initiative

First published: 08 December 2022

https://doi.org/10.1002/alz.12890

Abstract

Introduction

Although presynaptic loss measured by cerebrospinal fluid (CSF) growth-associated protein-43 (GAP-43) is significantly involved in Alzheimer's disease (AD), the sequential association between CSF GAP-43 and AD-typical neurodegeneration is poorly understood.

Methods

We compared baseline CSF GAP-43 levels (n = 730) and longitudinal CSF GAP-43 changes (n = 327) in various biological stages of AD, and investigated their relationships with cross-sectional and longitudinal measures of residual hippocampal volume, ¹⁸F-fluorodeoxyglucose PET, regional gray matter volume and cortical thickness, and cognition.

Results

Elevated CSF GAP43 levels were significantly associated with faster rates of hippocampal atrophy, AD-signature hypometabolism and cortical thinning, and middle temporal gray matter atrophy-related and AD-signature hypometabolism-related cognitive decline. In contrast, baseline levels of all these neurodegeneration biomarkers did not predict longitudinal CSF GAP-43 increases.

Discussion

These findings suggest that presynaptic loss may occur prior to neurodegeneration, highlighting the importance of lowing tau aggregation and tau-related synaptic dysfunction in elderly adults and AD patients.