Maqola

Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease

Shu‐Yi HuangDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaYa‐Ru ZhangDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaYu GuoDepartment of Neurology and National Center for Neurological Disorders Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Shanghai Medical College Fudan University Shanghai ChinaJing DuCentre for Healthy Brain Ageing (CHeBA) Discipline of Psychiatry and Mental Health School of Clinical Medicine UNSW Sydney New South Wales AustraliaPeng RenShanghai Center for Brain Science and Brain-Inspired TechnologyBang‐Sheng WuState Key Laboratory of Medical NeurobiologyJianfeng FengKey Laboratory of Computational Neuroscience and Brain‐Inspired Intelligence (Fudan University), Ministry of Education Shanghai ChinaAlzheimer's Disease Neuroimaging InitiativeDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaWei ChengShanghai Center for Brain Science and Brain-Inspired TechnologyJin‐Tai YuHuashan Hospital

2024en

ABI

Annotatsiya

INTRODUCTION: Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood. METHODS: Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) in participants with AD dementia (n = 47), mild cognitive impairment (MCI; n = 137), and normal controls (n = 235) from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: ALPS index was significantly lower in AD dementia than in MCI or controls. Lower ALPS index was significantly associated with faster changes in amyloid positron emission tomography (PET) burden and AD signature region of interest volume, higher risk of amyloid-positive transition and clinical progression, and faster rates of amyloid- and neurodegeneration-related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline were fully mediated by amyloid PET and brain atrophy. DISCUSSION: Glymphatic failure may precede amyloid pathology, and predicts amyloid deposition, neurodegeneration, and clinical progression in AD. HIGHLIGHTS: The analysis along the perivascular space (ALPS) index is reduced in patients with Alzheimer's disease (AD) dementia, prodromal AD, and preclinical AD. Lower ALPS index predicted accelerated amyloid beta (Aβ) positron emission tomography (PET) burden and Aβ-positive transition. The decrease in the ALPS index occurs before cerebrospinal fluid Aβ42 reaches the positive threshold. ALPS index predicted brain atrophy, clinical progression, and cognitive decline. Aβ PET and brain atrophy mediated the link of ALPS index with cognitive decline.

Hali tarjima qilinmagan

Identifikatorlar

DOI: 10.1002/alz.13789

Iqtiboslar va manbalar

2 ta iqtibos0 ta foydalanilgan manba