Functional Brain Network Connectivity Patterns Associated With Normal Cognition at Old-Age, Local β-amyloid, Tau, and APOE4

Abstract

Background: Integrity of functional brain networks is closely associated with maintained cognitive performance at old age. Consistently, both carrier status of Apolipoprotein E ε4 allele (APOE4), and age-related aggregation of Alzheimer's disease (AD) pathology result in altered brain network connectivity. The posterior cingulate and precuneus (PCP) is a node of particular interest due to its role in crucial memory processes. Moreover, the PCP is subject to the early aggregation of AD pathology. The current study aimed at characterizing brain network properties associated with unimpaired cognition in old aged adults. To determine the effects of age-related brain change and genetic risk for AD, pathological proteins β-amyloid and tau were measured by Positron-emission tomography (PET), PCP connectivity as a proxy of cognitive network integrity, and genetic risk by APOE4 carrier status. Methods: Fifty-seven cognitively unimpaired old-aged adults (MMSE = 29.20 ± 1.11; 73 ± 8.32 years) were administered 11C Pittsburgh Compound B and 18F Flutemetamol PET for assessing β-amyloid, and 18F AV-1451 PET for tau. Individual functional connectivity seed maps of the PCP were obtained by resting-state multiband BOLD functional MRI at 3-Tesla for increased temporal resolution. Voxelwise correlations between functional connectivity, β-amyloidand tau-PET were explored by Biological Parametric Mapping (BPM). Results: Local β-amyloid was associated with increased connectivity in frontal and parietal regions of the brain. Tau was linked to increased connectivity in more spatially distributed clusters in frontal, parietal, occipital, temporal, and cerebellar regions. A positive interaction was observable for APOE4 carrier status and functional connectivity with brain regions characterized by increased local β-amyloid and tau tracer retention.

A Systematic Review of the Association between Amyloid-β and τ Pathology with Functional Connectivity Alterations in the Alzheimer Dementia Spectrum Utilizing PET Scan and rsfMRI

“…Of the 4 studies applying seed-based connectivity, 2 indicated a positive association [20, 44] while 1 indicated a lower hippocampal FC in association with a higher τ burden in the inferior temporal cortex [21]. The last study mainly found a higher FC related to τ-PET covariance [17].…”

Local Functional MR Change Pattern and Its Association With Cognitive Function in Objectively-Defined Subtle Cognitive Decline

“…In the elderly with normal cognition, the connection between the occipital lobe and the posterior cingulate and precuneus is related to the tau protein, which may change in preclinical cognitive impairment (Quevenco et al, 2020). In patients with subjective cognitive decline, white matter damage across the frontal and occipital lobes was also found; this track is thought to be related to the gray matter damage such as the medial prefrontal cortex and posterior cingulate cortex in the early stage of AD (Luo et al, 2019).…”

Advances in the development paradigm of biosample‐based biosensors for early ultrasensitive detection of alzheimer’s disease

“…ApoE is an important cholesterol carrier that supports lipid transport and repairs brain injury. The presence of ApoE ɛ4 alleles in bio-fluids is strictly associated with genetic risk factors involved in the emergence of cerebral amyloid angiopathy and age-related cognitive impairments that cause late onset of AD [111]. ApoE joins with a number of receptors on the cell surface to deliver lipids and hydrophobic Aβ-peptides, thus introducing toxicity, causing synaptic dysfunction, and resulting in the deterioration or death of neurons that finally leads to AD.…”