Work

Unraveling the complexity of neurodegeneration: heterogeneous damage patterns of locus coeruleus and substantia nigra in Alzheimer's disease

Year: 2025

Type: article

Abstract: INTRODUCTION: Alzheimer's disease (AD) involves complex neurodegeneration in the locus coeruleus (LC) and substantia nigra (SN), critical brain regions affecting cognitive and emotional processes. METHODS: Using the National Alzheimer's Coordinating Center dataset of 11,583 participants, we conducted a multimodal analysis involving descriptive statistics, multifactorial regression, mediation analysis, and receiver operating characteristic curve assessment. RESULTS: LC degenerative changes (18.57%) significantly exceeded SN changes (4.69%). The LC demonstrated stronger correlations with psychiatric symptoms and cognitive impairment. High LC/low SN damage patterns showed the strongest associations with mild cognitive impairment (OR = 2.38) and AD (OR = 3.56). DISCUSSION: Our research reveals the heterogeneous degeneration patterns of LC and SN in AD, providing crucial insights into neurobiological mechanisms and potential strategies for early diagnosis and intervention. HIGHLIGHTS: This study provides a comprehensive framework for understanding the heterogeneous neurodegeneration patterns in AD through a detailed examination of the LC and SN. The research bridges the gap between neuroanatomical changes and neuropsychiatric symptoms, offering a more nuanced perspective on disease progression. Our findings challenge traditional linear models of neurodegeneration, emphasizing the complex and non-uniform nature of neural deterioration in AD. The study underscores the critical importance of investigating multiple neural nuclei to comprehensively understand neurodegenerative processes. By exploring the differential vulnerabilities of LC and SN, we provide new insights into potential targeted therapeutic interventions.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.70605

Authors: Chao Tang, Jiaxin Yang, Xiaoyang Lei, Ming Zhang, Yi Chen, Xiaoxue Peng, Dian He

Institution: Affiliated Hospital of Guizhou Medical University

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,200

Funders: Health Commission of Guizhou Province, National Institutes of Health, Genentech, National Major Science and Technology Projects of China, National Institute on Aging

Awards: G1020749929, G1024368718, G1048051091, G1058046096, G1069732457, G1075639496, G11426272, G117713310, G120189231, G1269895679, G1293354362, G1364373663, G1369195717, G1458362881, G1531775036, G1593128567, G1753564228, G1793654115, G1827328465, G1859882300, G2142974134, G2190936067, G2234397790, G2434699210, G253265979, G2622865600, G2632195949, G2675915175, G2742075923, G2887984396, G3284295768, G333817976, G3430734602, G343469054, G348743638, G3703765782, G371566797, G3818147302, G3952091757, G415047313, G4186766937, Nevada Exploratory Alzheimer's Disease Research Center (NVEADRC), G4390231255, G4622257776, UAB Alzheimer's Disease Research Center, G504619356, G5056789898, G5640525220, G6250057130, New Mexico Alzheimer's Disease Research Center, G726963014, G7380798711, G76412088, G816726602, G855012155, G8824643644, G9000000175, G9000000449, G9000004438, G9000011165, G9000011571, G9000015010, G9000015941, G9000038514, G9000041566, G9000044512, G9000056371, G9000059605, G9000060917, G9000063279, G9000065392, G9000065952, G9000079798, G9000081013, G9000082286, G9000085578, G9000087139, G9000087364, G9000091371, G9000100769, G9000112075, G9000114108, G9000115163, G9000134521, G9000148901, G9000182597, G9000183948, G9000208313, G9000224607, G9000226412, G9000254440, G9000266300, G9000271511, G9000290608, G9000305967, G9000315395, G9000320238, G9000330862, G9000331231, G9000332211, G9000341970, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Joint Estimate Diffusion Imaging (JEDI) for improved Tissue Characterization and Neural Connectivity in Aging and Alzheimer's Disease, University of Kansas Alzheimer's Disease Research Center (KU ADRC), Alzheimer's Disease Research Center, Johns Hopkins Alzheimer's Disease Research Center, Stanford Alzheimer's Disease Research Center, University of Washington Alzheimer's Disease Research Center, Goizueta Alzheimer's Disease Research Center

OpenAlex ID: W4413906657

FWCI: 2.453

Cites: 93

Cited by: 4

Related to: 10