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

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title = "Pathological drivers of neurodegeneration in suspected non-Alzheimer{\textquoteright}s disease pathophysiology",
abstract = "Background: Little is known about the heterogeneous etiology of suspected non-Alzheimer{\textquoteright}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.",
keywords = "Hippocampus, Limbic-predominant age-related TDP-43 encephalopathy, Medial temporal lobe, Neurodegeneration, Neurodegenerative pathologies, Neuropathologies diagnosis, Primary age-related tauopathy, Suspected non-Alzheimer{\textquoteright}s pathophysiology",
author = "Wisse, {L. E.M.} and {de Flores}, R. and L. Xie and Das, {S. R.} and McMillan, {C. T.} and Trojanowski, {J. Q.} and M. Grossman and Lee, {E. B.} and D. Irwin and Yushkevich, {P. A.} and Wolk, {D. A.} and {Alzheimer's Disease Neuroimaging Initiative}",
year = "2021",
month = dec,
doi = "10.1186/s13195-021-00835-2",
language = "English",
volume = "13",
journal = "Alzheimer's Research & Therapy",
issn = "1758-9193",
publisher = "BioMed Central (BMC)",