Abstract
INTRODUCTION
Alzheimer’s disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)–immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.
METHODS
We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non–NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).
RESULTS
There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.
DISCUSSION
These results suggest that there are subregion-specific proteomic differences among the neurons of these disorders, which appear to be influenced to a large degree by the presence of hippocampal Aβ. These proteomic differences may play a role in the differing hippocampal p-tau distribution and pathogenesis of these disorders.
Highlights
Alzheimer’s disease neuropathologic change (ADNC), possible primary age-related tauopathy (PART), definite PART, and chronic traumatic encephalopathy (CTE) can be differentiated based on the proteomic composition of their neurofibrillary tangle (NFT)- and non–NFT-bearing neurons.
The proteome of these NFT- and non–NFT-bearing neurons is largely correlated with the presence or absence of amyloid beta (Aβ).
Neurons in CTE and definite PART (Aβ-independent pathologies) share numerous proteomic similarities that distinguish them from ADNC and possible PART (Aβ-positive pathologies).
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This post is Copyright: Timothy E. Richardson,
Miranda E. Orr,
Timothy C. Orr,
Susan K. Rohde,
Alexander J. Ehrenberg,
Emma L. Thorn,
Thomas D. Christie,
Victoria Flores‐Almazan,
Robina Afzal,
Claudia De Sanctis,
Carolina Maldonado‐Díaz,
Satomi Hiya,
Leyla Canbeldek,
Lakshmi Shree Kulumani Mahadevan,
Cheyanne Slocum,
Jorge Samanamud,
Kevin Clare,
Nicholas Scibetta,
Raquel T. Yokoda,
Daniel Koenigsberg,
Gabriel A. Marx,
Justin Kauffman,
Adam Goldstein,
Enna Selmanovic,
Eleanor Drummond,
Thomas Wisniewski,
Charles L. White III,
Alison M. Goate,
John F. Crary,
Kurt Farrell,
Michael L. Alosco,
Jesse Mez,
Ann C. McKee,
Thor D. Stein,
Kevin F. Bieniek,
Tiffany F. Kautz,
Elena V. Daoud,
Jamie M. Walker | December 31, 2024