Year: 2014
Type: article
Study design: Observational Study
Abstract: To assess the relationships between core cerebrospinal fluid (CSF) biomarkers and cortical thickness (CTh) in preclinical Alzheimer's Disease (AD). Cross-sectional study. Fifty-three cognitively preserved individuals from Hospital Sant Pau (HSP) and 131 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent structural 3T-MRI and lumbar puncture. A subgroup of ADNI under 75 years was defined (ADNI-young). CSF amyloid 1-42 (Aß1-42) and phospho-tau (p-tau181p) levels were measured by ELISA (HSP) or Luminex (ADNI) assays. Samples were dichotomized using published cut-offs (Aß+/Aß- and p-tau+/ptau-). CTh was measured by Freesurfer. CTh difference maps were derived from correlation and interaction analyses. CSF Aß1-42 levels showed a negative correlation with CTh in the 50-75 year range (HSP and ADNI-young) but not in the older group (ADNI). Stratified analyses in ADNI and ADNI-young showed the negative correlation of Aß1-42 and CTh was dependent on CSF p-tau181p. This negative correlation was found in p-tau- subjects (p<0.05 corrected) but not in p-tau+. Conversely, p-tau181p correlated negatively with CTh in Aß+, but not in Aß- in ADNI and ADNI-young. These results were confirmed in the interaction analyses. Interactions between markers determine a two-phase phenomenon of pathological cortical thickening in relation to decreasing CSF Aß1-42 followed by atrophy once the synergistic toxic effect with p-tau predominates. These interactions should be considered in clinical trials with anti-amyloid drugs, both for the use of amyloid imaging alone in the selection of patients and for the use of MRI as a surrogate marker of efficacy.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2007043350