Pathological drivers of neurodegeneration in suspected non-Alzheimer’s disease pathophysiology

Alzheimer’s Research & Therapy

on behalf of the Alzheimer’s Disease NeuroImaging Initiative¹  E. B. Lee²  J. Q. Trojanowski²  D. Irwin²  L. E. M. Wisse³  C. T. McMillan⁴  M. Grossman⁴  L. Xie⁵  P. A. Yushkevich⁵  D. A. Wolk⁶  S. R. Das⁶  R. de Flores⁷ 

[1] ;Center for Neurodegenerative Disease Research, University of Pennsylvania;Department of Diagnostic Radiology, Lund University;Penn FTD Center, Department of Neurology, University of Pennsylvania;Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania;Penn Memory Center, Department of Neurology, University of Pennsylvania;Université Normandie, Inserm, Université de Caen-Normandie, Inserm UMR-S U1237, GIP Cyceron;

关键词: Suspected non-Alzheimer’s pathophysiology;    Neuropathologies diagnosis;    Neurodegenerative pathologies;    Hippocampus;    Medial temporal lobe;    Neurodegeneration;   

DOI  :  10.1186/s13195-021-00835-2

来源: DOAJ

【 摘 要 】

Abstract Background Little is known about the heterogeneous etiology of suspected non-Alzheimer’s pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjects. Methods Subjects with antemortem MRI and autopsy data were selected from ADNI (n=63) and the University of Pennsylvania (n=156). Pathological diagnoses and semi-quantitative scores of MTL tau, neuritic plaques, α-synuclein, and TDP-43 pathology and MTL structural MRI measures from antemortem T1-weighted MRI scans were obtained. β-amyloid status (A+/A−) was determined by CERAD score and neurodegeneration status (N+/N−) by hippocampal volume. Results SNAP reflects a heterogeneous group of pathological diagnoses. In ADNI, SNAP (A−N+) had significantly more neuropathological diagnoses than A+N+. In the A− group, tau pathology was associated with hippocampal, entorhinal cortex, and Brodmann area 35 volume/thickness and TDP-43 pathology with hippocampal volume. Conclusion SNAP had a heterogeneous profile with more mixed pathologies than A+N+. Moreover, a role for TDP-43 and tau pathology in driving MTL neurodegeneration in the absence of β-amyloid was supported.

【 授权许可】

Unknown