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Cerebral amyloid‐β load is associated with neurodegeneration and gliosis: Mediation by p‐tau and interactions with risk factors early in the Alzheimer's continuum
Author(s) -
Salvadó Gemma,
MilàAlomà Marta,
Shekari Mahnaz,
Minguillon Carolina,
Fauria Karine,
NiñerolaBaizán Aida,
Perissinotti Andrés,
Kollmorgen Gwendlyn,
Buckley Christopher,
Farrar Gill,
Zetterberg Henrik,
Blennow Kaj,
SuárezCalvet Marc,
Molinuevo José Luis,
Gispert Juan Domingo
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12245
Subject(s) - neurodegeneration , neuroinflammation , neurogranin , neuroscience , psychology , gliosis , tauopathy , cerebrospinal fluid , medicine , disease , pathology , biology , signal transduction , biochemistry , protein kinase c
The association between cerebral amyloid‐β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages. Methods In 318 cognitively unimpaired participants, we assessed the association between amyloid‐β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiological pathways. Interactions by Alzheimer's disease risk factors (age, sex and APOE‐ε4 ), and the mediation effect of tau and neurodegeneration were also investigated. Results Centiloids were positively associated with CSF biomarkers of tau pathology (p‐tau), neurodegeneration (t‐tau, NfL), synaptic dysfunction (neurogranin) and neuroinflammation (YKL‐40, GFAP, sTREM2), presenting interactions with age (p‐tau, t‐tau, neurogranin) and sex (sTREM2, NfL). Most of these associations were mediated by p‐tau, except for NfL. The interaction between sex and amyloid‐β on sTREM2 and NfL was also tau‐independent. Discussion Early amyloid‐β accumulation has a tau‐independent effect on neurodegeneration and a tau‐dependent effect on neuroinflammation. Besides, sex has a modifier effect on these associations independent of tau.