Sa Zhou

All Publications

• Relationships between neuropsychiatric symptoms, subtypes of astrocyte activities, and brain pathologies in Alzheimer's disease and Parkinson's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association Li, O. Y., Shin, S., Zhou, S., Turnbull, A., Lin, F. V. 2025; 21 (5): e70242

  Abstract

  Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative diseases (NDs). This study examined astrocytic contributions to neuropsychiatric symptoms (NPS), focusing on astrocytic protein activity and its relationship with NPS severity, accounting for clinical and pathological features of NDs.Cerebrospinal astrocytic proteins (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and aquaporin-4 [AQP4]) from Alzheimer's Disease Neuroimaging Initiative (ADNI) (AD) and Parkinson's Progression Markers Initiative (PPMI) (PD) were analyzed using K-means clustering. Six NPS domains, ND-specific pathologies (amyloid-beta/Aβ for AD, alpha-synuclein/αSyn for PD), and nonspecific pathology (phosphorylated tau/ptau) were assessed.In both samples, three astrocytic clusters were identified, and the "highYKL|lowOthers" cluster (high YKL-40, low GFAP/AQP4) consistently showed lower ptau and NPS severity compared to the "highAll" cluster (high GFAP, YKL-40, AQP4). In PPMI, the "highYKL|lowOthers" cluster also attenuated the relationship between αSyn and NPS compared to the "highAll" cluster.Astrocytic activity relates to NPS, highlighting astrocytic proteins as potential therapeutic targets for NPS in NDs.Astrocytic protein clusters were linked to NPS severity in AD and PD cohorts. The "highYKL|lowOthers" cluster showed lower ptau and NPS severity than "allhigh" cluster in AD and PD cohorts. Astrocytic proteins may serve as therapeutic targets for managing NPS in NDs.

  View details for DOI 10.1002/alz.70242

  View details for PubMedID 40390204

  View details for PubMedCentralID PMC12089078

• Biomarkers. Alzheimer's & dementia : the journal of the Alzheimer's Association Zhou, S., Lin, F. V. 2024; 20 Suppl 2: e088668

  Abstract

  To maintain local dynamic stability (LDS), both cognitively and physically, without being interfered with by internal or external disturbance is important for functional independence but declines as ages. However, some older adults are capable of high dual-functional LDS. Understanding the brain differences between these older adults and their counterparts may help discover protective mechanisms for functional independence in old age. The purpose of the study was to compare the brain topology between older adults with heterogenous dual-functional LDS.Cognitively and physically healthy older individuals (n = 52) were recruited and categorized into four groups (low cognitive/low physical, low cognitive/high physical, high cognitive/low physical, and high cognitive/high physical LDS groups) based on the intra-individual variability of performance in selected cognitive and physical tasks relying on speed processing and attention. Brain topology was measured via diffusion tensor imaging and quantified with clustering coefficients reflecting segregation and characteristic path lengths reflecting integration, respectively, based on graph theory methods.After correcting for multi-comparison, the high dual-functional LDS group exhibited significantly higher integration between the inferior frontal and postcentral areas but lower integration between the frontal and temporary areas within the left hemisphere, compared to the other three low cognitive/physical stability groups.Integration in selective brain networks may contribute to maintaining the dual-functional LDS in older adults.

  View details for DOI 10.1002/alz.088668

  View details for PubMedID 39785575

• Profiles of brain topology for dual-functional stability in old age. GeroScience Zhou, S., Anthony, M., Adeli, E., Lin, F. V. 2024

  Abstract

  Dual-functional stability (DFS) in cognitive and physical abilities is important for successful aging. This study examines the brain topology profiles that underpin high DFS in older adults by testing two hypotheses: (1) older adults with high DFS would exhibit a unique brain organization that preserves their physical and cognitive functions across various tasks, and (2) any individuals with this distinct brain topology would consistently show high DFS. We analyzed two cohorts of cognitively and physically healthy older adults from the UK (Cam-CAN, n = 79) and the US (CF, n = 48) using neuroimaging data and a combination of cognitive and physical tasks. Variability in DFS was characterized using k-mean clustering for intra-individual variability (IIV) in cognitive and physical tasks. Graph theory analyses of diffusion tensor imaging connectomes were used to assess brain network segregation and integration through clustering coefficients (CCs) and shortest path lengths (PLs). Using support vector machine and regression, brain topology features, derived from PLs + CCs, differentiated the high DFS subgroup from low and mix DFS subgroups with accuracies of 65.82% and 84.78% in Cam-CAN and CF samples, respectively, which predicted cross-task DFS score in CF samples at 58.06% and 70.53% for cognitive and physical stability, respectively. Results showed distinctive neural correlates associated with high DFS, notably varying regional brain segregation and integration within critical areas such as the insula, frontal pole, and temporal pole. The identified brain topology profiles suggest a distinctive neural basis for DFS, a trait indicative of successful aging. These insights offer a foundation for future research to explore targeted interventions that could enhance cognitive and physical resilience in older adults, promoting a healthier and more functional lifespan.

  View details for DOI 10.1007/s11357-024-01396-6

  View details for PubMedID 39432149

  View details for PubMedCentralID 7058488