Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease

Abstract

In Alzheimer's disease (AD), pathologic tau gradually progresses from initially circumscribed predilection regions to closely connected cortical regions. The pattern of tau-deposition is of critical importance for the clinical expression of AD, but the factors that underlie region-dependent susceptibility and resistance to tau pathology remain elusive. Motivated by brain-autopsy findings suggesting late thinly myelinated regions are the first to develop tau pathology, we investigated whether the level of myelination in fiber-tracts and cortex is predictive of region-specific tau accumulation. To address this hypothesis, we combined MRI-derived template of normative myelin distribution with tau-PET imaging from two independent samples of AD-biomarker characterized participants. We found that higher myelinated cortical regions show lower tau-PET uptake in spatially corresponding areas and regions connected by highly myelinated fiber-tracts show lower rates of tau spreading. These findings were independent of amyloid-PET levels. Together, our findings suggest that higher myelination is an important resistance factor against tau pathology in AD.

Histaminergic neurotransmission in aging and Alzheimer's disease: A review of therapeutic opportunities and gaps

“…Unmyelinated or poorly myelinated neurons are prone to develop NFTs and are vulnerable to oxidative stress (OS). 44 , 45 HA N s are predominantly unmyelinated and send long axonal projections to various brain parts. In AD, tau NFTs accumulate in the brainstem before they appear in the entorhinal cortex, the first cortical region to accumulate NFTs.…”