Tau and synaptic biomarkers but not amyloid‐β are associated with cerebral perfusion in the Alzheimer’s disease spectrum

Abstract

AbstractBackgroundA large body of evidence has shown decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD). However, the link between CBF and the primary AD pathologies as well as synaptic integrity remains unclear.MethodBaseline CBF was measured using arterial spin labeling (ASL) in a 3T MRI scanner in 137 cognitively unimpaired individuals with and without amyloid‐beta (Aβ) pathology, in addition to 119 cognitively impaired participants with mild cognitive impairment or AD dementia who all had Aβ pathology from the Swedish BioFINDER‐2 study. Aβ and tau pathology were measured using cerebrospinal fluid (CSF) levels of Aβ42/40 and amyloid‐PET, as well as CSF P‐tau217 levels and tau‐PET, respectively. Synaptic integrity was estimated using CSF neuronal pentraxin 2 (NPTX2)/total‐tau (T‐tau) ratio. Voxel‐wise and linear regression analyses in a set of a priori defined regions of interest (ROIs) were used to assess between‐group differences in CBF, and the relationship between CBF and the PET and CSF measures.ResultCBF was decreased in the lateral temporal, lateral and medial parietal and superior lateral occipital cortex in the cognitively impaired compared to cognitively unimpaired individuals, independent of Aβ pathology. In contrast, no differences were found in CBF between the cognitively unimpaired groups with and without Aβ pathology. Further, in cognitively unimpaired individuals, CBF was not associated with any of the biomarkers of Aβ, tau or synaptic integrity. However, in individuals on the AD spectrum i.e., those with Aβ pathology regardless of their cognitive status, an inverse association was observed between CBF and tau pathology (tau‐PET and CSF P‐tau217), but not Aβ pathology (CSF Aβ42/40 and amyloid‐PET), predominantly in the occipito‐temporo‐parietal regions. Moreover, lower NPTX2/T‐tau was associated with hypoperfusion in similar regions.ConclusionThese findings suggest that tau‐tangle pathology and synaptic degeneration are more closely associated with overt changes in CBF than Aβ pathology. This supports the notion that blood flow changes, at least those measured by ASL, are not an early event associated with the build‐up of Aβ pathology during the preclinical phases of AD.