Basal forebrain atrophy and tau pathology are correlated in prodromal AD

Abstract

AbstractBackgroundDegeneration of cholinergic basal forebrain (BF) neurons play a role in the progression of Alzheimer’s disease (AD), with atrophy of the BF preceding cognitive dysfunction. Here, we investigated whether the presence of Ab and/or Tau PET tracer retention in cognitively normal elderly controls was associated with BF atrophy.MethodCognitively healthy participants (N = 134, 49% male) from the AIBL cohort underwent 3T MRI and amyloid (18F‐NAV4694), and Tau (18F‐MK6240) PET scans. PET images were spatially normalised and scaled to the cerebellar cortex using CapAIBL. An amyloid‐positive scan (Aβ+) was defined by cortical retention of ≥20 centiloids. Tau positivity (Tau+) was defined as the average mesial‐temporal lobe SUVR greater than two standard deviations of the Aβ‐ CN subjects for tau. BF volumes were generated from T1w MRIs using an SPM8‐based pipeline and cytoarchitectonic atlas that define BF nuclei Ch1 to 4. Models were corrected for intracranial volume, grey matter, gender and age. Statistical analysis was implemented in Rstudio using general linear models (GLM).ResultSubjects were placed into 3 groups (age, 75.03 ± 5.22 years, was not different between groups) consisting of 103 Aβ‐/Tau‐ subjects, 19 Aβ+/Tau‐ subjects and 12 Aβ+/Tau+ subjects. Although not cognitively impaired, the Aβ+/Tau+ cohort had lower MMSE and higher CDR scores than the Aβ‐/Tau‐ group. After correction for intracranial volume, gray matter and age, volumes of the entire BF and BF subregions were significantly smaller in the Aβ+/Tau+ group than the Aβ+/Tau‐ group (Figure 1, p < 0.05). BF volumes for NC Aβ‐/Tau‐ and NC Aβ+/Tau‐ groups were not different, indicating that BF atrophy and Tau pathology are strongly related.ConclusionThese findings are consistent with previous studies of cognitively impaired populations and suggest that in prodromal AD, atrophy in the BF occurs in parallel with the development of tau pathology and cognitive decline. We are investigating longitudinal changes in this population. Figure 1. Box plot representing comparisons between the three groups in terms of volumetry of BF (A) Ch4 sum ( Ch4 posterior and Ch4 anterior compartments) and (B) Ch1‐3 sum after the correction of intracranial volume and age by general linear models.