P4‐341: Alzheimer risk variant complement component (3b/4b) receptor‐1 (CR1) and brain function during aging
Year: 2011
Type: article
Abstract: Recent studies have identified polymorphisms in the complement component (3b/4b) receptor-1 (CR1) gene to be associated with risk for Alzheimer's disease (AD). We previously identified complement proteins as plasma biomarkers of AD associated with brain atrophy in patients and amyloid burden in non-demented older individuals. We examined the effect of the rs3818361 single nucleotide polymorphism in the CR1 gene on longitudinal changes in resting state regional cerebral blood flow (rCBF) in cognitively normal older individuals in the Baltimore Longitudinal Study of Aging (BLSA). Longitudinal 15O-water PET measurements of rCBF were available at baseline and 7 annual follow-up visits in 85 BLSA participants (mean age at baseline; 69.3 ± 7.3 years), in whom genome-wide genotyping data were collected. Neuropsychological testing measured performance in six cognitive domains including memory. Allele frequencies in the CR1 rs3818361 polymorphism were C/C in 60 subjects (70.6%) and C/T in 25 subjects (29.4%). The two groups (CC and CT) did not differ significantly in age at baseline, education or APOE e4 status. Mini-Mental State Examination scores and annual rates of change in domain-specific cognitive performance also did not differ significantly between groups. We observed significant longitudinal changes in rCBF in several brain regions in carriers of the AD risk allele (T) of rs3818361 relative to non-carriers. Longitudinal increments in rCBF were observed in the right and left insula, orbitofrontal cortex, medial frontal gyrus, brainstem and thalamus. Longitudinal decreases in rCBF were observed in the right and left middle frontal gyri, inferior parietal cortex and precuneus. These associations remained significant after co-varying for age, sex and APOE e4 status. The AD risk variant of CR1 influences longitudinal changes in rCBF in brain regions intrinsic to memory processes in cognitively normal older individuals. The regions involved are those vulnerable to accumulation of beta amyloid and include components of the default mode network known to be disrupted by amyloid deposition even in non-demented elderly. We propose that these observed changes in neuronal activity represent both perturbations in neural function as well as compensatory changes in key memory circuits that are required to maintain normal cognition in at-risk individuals during aging.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2031188131