Amyloidosis at Putamen Predicts Vulnerability to Alzheimer’s Disease

Abstract

AbstractBackgroundUsing merely cortical amyloid burden in a binary approach was commonly adopted for determining if an individual is under AD pathology in both clinical trials and basic research. Subcortical amyloid, compared to cortical amyloid, showed a larger inter‐subject heterogeneity, which may provide valuable insights to their vulnerability to Alzheimer’s disease beyond cortical amyloid.MethodA total of 1344 individuals from ADNI database had 18F‐AV45 amyloid PET scans available. Regional AV45 signal was computed by averaging the signal from gray matter voxels in each region and then normalized to the mean signal in the composite reference region [1, 2]. The cortical AV45 was averaged over extensive regions consisting of frontal, anterior/posterior cingulate, lateral parietal, and lateral temporal regions. The AV45 signal in the subcortex, including putamen and caudate, were also computed. Only the participants under AD pathology, determined based on cortical amyloid positivity, were included in the analysis. The association analysis between subcortical AV45 and cognition was conducted before and after adjusting cortical AV45. A linear fitting of cortical AV45 and AV45 at putamen was conducted and participants were categorized into high (HighP), middle (MidP) and low (LowP) putamen amyloid group thresholded with ±0.5 standardized residuals. Statistical analysis was carried out to evaluate the difference of clinical diagnosis, hippocampal volume and APOE ε4 genotype. The relevance of amyloid at putamen with the rate of cognitive decline was examined.ResultPutamen, compared to caudate, had a stronger association with ADAS‐cog13 and MoCA, such an association remained exist after adjusting cortical AV45. Despite distinct AV45 at putamen, participants in LowP, MidP and HighP groups had no cortical AV45 difference. The AV45 at putamen was significantly higher in individuals with more ε4 alleles (ε4 homozygous > ε4 heterozygous > non‐ ε4) and more advance clinical stages (Dementia > MCI > CN). The individuals with higher AV45 at putamen had smaller hippocampal volume and faster cognitive decline.ConclusionOur finding suggested that amyloidosis at putamen is a valuable imaging marker beyond cortical amyloid in predicting if a participant is more vulnerable to Alzheimer’s dementia.