α‐synuclein pathology drives region‐specific tau deposition
- 1Department of Radiology Brain Health Imaging Institute Weill Cornell Medicine New York New York USA
Abstract
INTRODUCTION: Dementia with Lewy bodies (DLB) is a common but underdiagnosed neurodegenerative disease associated with α‐synuclein pathology. Clinically, DLB is characterized by early motor dysfunction and psychiatric symptoms, in contrast to early memory decline typical of Alzheimer's disease (AD). Lewy body and AD pathology commonly co‐occur. It remains unclear how α‐synuclein pathology, either alone or in combination with AD pathology, produces clinical features considered distinctive of synucleinopathy.
METHODS: We analyzed 531 Alzheimer's Disease Neuroimaging Initiative participants using neuroimaging to compare tau deposition patterns between α‐synuclein–positive and α‐synuclein–negative individuals.
RESULTS: α‐synuclein–positive individuals showed significantly greater tau deposition in basal ganglia (BG), insula, and medial temporal lobe (MTL). Increased tau burden in these regions correlated with more severe psychiatric symptoms and slower reaction times. These associations were present only in the α‐synuclein–positive group.
DISCUSSION: These results suggest that α‐synuclein pathology is associated with region‐specific tau positron emission tomography abnormalities that map onto core clinical features of synucleinopathy.
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BibTeX
@article{hojjati2026αsynuclein,
title = {{α‐synuclein pathology drives region‐specific tau deposition}},
author = {Seyed Hani Hojjati and Gloria C. Chiang and Xiuyuan Hugh Wang and Mohammad Khalafi and Sudhin Shah and Liangdong Zhou and Samantha Keil and Lidia Glodzik and Laura Beth J. McIntire and Emily Tanzi and Farnia Feiz and Tom Maloney and Yi Li and Tracy A. Butler and for the Alzheimer's Disease Neuroimaging Initiative},
journal = {Alzheimer's \& Dementia},
year = {2026},
month = oct,
doi = {10.1002/alz.71932},
url = {https://doi.org/10.1002/alz.71932},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - α‐synuclein pathology drives region‐specific tau deposition
AU - Seyed Hani Hojjati
AU - Gloria C. Chiang
AU - Xiuyuan Hugh Wang
AU - Mohammad Khalafi
AU - Sudhin Shah
AU - Liangdong Zhou
AU - Samantha Keil
AU - Lidia Glodzik
AU - Laura Beth J. McIntire
AU - Emily Tanzi
AU - Farnia Feiz
AU - Tom Maloney
AU - Yi Li
AU - Tracy A. Butler
AU - for the Alzheimer's Disease Neuroimaging Initiative
PY - 2026
DA - 2026/10/01
JO - Alzheimer's & Dementia
DO - 10.1002/alz.71932
UR - https://doi.org/10.1002/alz.71932
AB - INTRODUCTION: Dementia with Lewy bodies (DLB) is a common but underdiagnosed neurodegenerative disease associated with α‐synuclein pathology. Clinically, DLB is characterized by early motor dysfunction and psychiatric symptoms, in contrast to early memory decline typical of Alzheimer's disease (AD). Lewy body and AD pathology commonly co‐occur. It remains unclear how α‐synuclein pathology, either alone or in combination with AD pathology, produces clinical features considered distinctive of synucleinopathy. METHODS: We analyzed 531 Alzheimer's Disease Neuroimaging Initiative participants using neuroimaging to compare tau deposition patterns between α‐synuclein–positive and α‐synuclein–negative individuals. RESULTS: α‐synuclein–positive individuals showed significantly greater tau deposition in basal ganglia (BG), insula, and medial temporal lobe (MTL). Increased tau burden in these regions correlated with more severe psychiatric symptoms and slower reaction times. These associations were present only in the α‐synuclein–positive group. DISCUSSION: These results suggest that α‐synuclein pathology is associated with region‐specific tau positron emission tomography abnormalities that map onto core clinical features of synucleinopathy.
SN - 1552-5260
SN - 1552-5279
ER -