The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer's disease.

DOI
Publisher DOI
PubMed ID
37137254
Abstract
PURPOSE

Left-right asymmetry, an important feature of brain development, has been implicated in neurodegenerative diseases, although it's less discussed in typical Alzheimer's disease (AD). We sought to investigate whether asymmetric tau deposition plays a potential role in AD heterogeneity.

METHODS

Two independent cohorts consisting of patients with mild cognitive impairment due to AD and AD dementia with tau PET imaging were enrolled [the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with 18F-Flortaucipir, the Shanghai Memory Study (SMS) cohort with 18F-Florzolotau]. Based on the absolute global tau interhemispheric differences, each cohort was divided into two groups (asymmetric versus symmetric tau distribution). The two groups were cross-sectionally compared in terms of demographic, cognitive characteristics, and pathological burden. The cognitive decline trajectories were analyzed longitudinally.

RESULTS

Fourteen (23.3%) and 42 (48.3%) patients in the ADNI and SMS cohorts showed an asymmetric tau distribution, respectively. An asymmetric tau distribution was associated with an earlier age at disease onset (proportion of early-onset AD: ADNI/SMS/combined cohorts, p = 0.093/0.026/0.001) and more severe pathological burden (i.e., global tau burden: ADNI/SMS cohorts, p < 0.001/= 0.007). And patients with an asymmetric tau distribution were characterized by a steeper cognitive decline longitudinally (i.e., the annual decline of Mini-Mental Status Examination score: ADNI/SMS/combined cohorts, p = 0.053 / 0.035 / < 0.001).

CONCLUSIONS

Asymmetry in tau deposition, which may be associated with an earlier age at onset, more severe pathological burden, and a steeper cognitive decline, is potentially an important characteristic of AD heterogeneity.
Date Issued
2023-04-28
Publication Type
Article
Subject(s)
Subjects
Age Alzheimer’s disease Asymmetry Positron emission tomography Prognosis Tau
Language(s)
en
Author(s)
Zhang, Zhengwei
Wu, Ping
Liang, Xiaoniu
Zhang, Huiwei
Yen, Tzu-Chen
Ding, Saineng
Wang, Min
Xiao, Zhenxu
Guan, Yihui
Zuo, Chuantao
Zhao, Qianhua
Additional Credits
Journal
NeuroImage: Clinical
Publisher
Elsevier
ISSN
2213-1582
Access(Rights)
open.access
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