ArticleAlzheimer's research & therapy2022
P-tau subgroups in AD relate to distinct amyloid production and synaptic integrity profiles.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 21 citations in OpenAlex.
- Cerebrospinal Fluid Amyloid-β Biomarkers Predict Future Hemorrhage in Patients with Cerebral Amyloid Angiopathy.Annals of neurology · 2026Article
- CSF proteomic profiles related to cognitive decline in MCI A+ depend on tau levels.Brain : a journal of neurology · 2025Article
- Cerium-doped Prussian blue biomimetic nanozyme as an amplified pyroptosis inhibitor mitigate Aβ oligomer-induced neurotoxicity in Alzheimer's disease.Journal of nanobiotechnology · 2025Article
- The impact of high-intensity interval training on cerebrovascular function in the APP/PS1 mice.Frontiers in aging · 2025Article
- Plasma vesicle-associated membrane protein 2 and glial fibrillary acidic protein associate with synaptic density in older adults without dementia.Brain communications · 2025Article
- Article
- Cellular and pathological functions of tau.Nature reviews. Molecular cell biology · 2024Review
- Secretome Analysis Using Affinity Proteomics and Immunoassays: A Focus on Tumor Biology.Molecular & cellular proteomics : MCP · 2024Review
- Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles.Nature aging · 2024Article
- Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer's disease continuum.Alzheimer's research & therapy · 2023Article
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10 authors at 6 institutions in 3 countries.
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Abstract
backgroundWe previously identified four Alzheimer's disease (AD) subgroups with increasingly higher cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 181 (p-tau). These subgroups included individuals across the cognitive spectrum, suggesting p-tau subgroups could reflect distinct biological changes in AD, rather than disease severity. Therefore, in the current study, we further investigated which potential processes may be related with p-tau subgroups, by comparing individuals on CSF markers for presynaptic structure [vesicle-associated membrane protein 2 (VAMP2)], postsynaptic structure [neurogranin (NRGN)], axonal damage [neurofilament light (NfL)], and amyloid production [beta-secretase 1 (BACE1) and amyloid-beta 1-40 (Aβ40)].
methodsWe selected 348 amyloid-positive (A+) individuals (53 preclinical, 102 prodromal, 193 AD dementia) and 112 amyloid-negative (A-) cognitively normal (CN) individuals from the Amsterdam Dementia Cohort (ADC). Individuals were labeled according to their p-tau subgroup (subgroup 1: p-tau ≤ 56 pg/ml; subgroup 2: 57-96 pg/ml; subgroup 3: 97-159 pg/ml; subgroup 4: > 159 pg/ml). CSF protein levels were measured with ELISA (NRGN, BACE1, Aβ40, NfL) or single-molecule array (Simoa) (VAMP2). We tested whether protein levels differed between the p-tau subgroups within A+ individuals with linear models corrected for age and sex and whether disease stage influenced these relationships.
resultsAmong A+ individuals, higher p-tau subgroups showed a higher percentage of AD dementia [subgroup 1: n = 41/94 (44%); subgroup 2: n = 81/147 (55%); subgroup 3: n = 59/89 (66%); subgroup 4: n = 7/11 (64%)]. Relative to controls, subgroup 1 showed reduced CSF levels of BACE1, Aβ40, and VAMP2 and higher levels of NfL. Subgroups 2 to 4 showed gradually increased CSF levels of all measured proteins, either across the first three (NfL and Aβ40) or across all subgroups (VAMP2, NRGN, BACE1). The associations did not depend on the clinical stage (interaction p-values ranging between 0.19 and 0.87).
conclusionsThe results suggest that biological heterogeneity in p-tau levels in AD is related to amyloid metabolism and synaptic integrity independent of clinical stage. Biomarkers reflecting amyloid metabolism and synaptic integrity may be useful outcome measures in clinical trials targeting tau pathology.
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