Interaction of Age and APOE Genotype on Cerebral Blood Flow at Rest

Abstract

We investigated the impact of APOE genotype on cerebral blood flow (CBF) in older and younger adults. Forty cognitively normal older adults (16 ε4 carriers, 24 non-ε4 carriers) and 30 younger adults (15 ε4 carriers, 15 non-ε4 carriers) completed a resting-state whole-brain pulsed arterial spin labeling magnetic resonance scan. Main effects of aging were demonstrated wherein older adults had decreased gray matter CBF corrected for partial volume effects compared to younger adults in widespread brain regions. Main effects of APOE genotype were also observed wherein ε4 carriers displayed greater CBF in the left lingual gyrus and precuneus than non-carriers. An interaction between age and APOE genotype in the left anterior cingulate cortex (ACC) was characterized by reduced CBF in older ε4 carriers and increased CBF in young ε4 carriers. Increased CBF in the left ACC resulting from the interaction of age group and APOE genotype was positively correlated with executive functioning in young ε4 adults (r = 0.61, p = 0.04). Results demonstrate APOE genotype differentially impacts cerebrovascular function across the lifespan and may modify the relationship between CBF and cognition. Findings may partially support suggestions that the gene exerts antagonistic pleiotropic effects.

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

“…ePiB was negatively correlated with age in PiB-positive subjects but not in PiB-negative subjects which is a new finding. An interaction of ApoE4 and age on CBF has been described (Wierenga et al, 2013) that indirectly supports our findings as ApoE4 is the strongest predictor of high amyloid deposition in healthy subjects (Mielke et al, 2012), which we also found in our sample. Hypermetabolism associated with amyloid load has been demonstrated before in cognitively healthy subjects .…”

“…In the hypothesis of the amyloid cascade and in a recently formulated hypothetical biomarker model, they were put downstream to amyloid and tau deposition . However, studies in subjects at risk of AD, for example, young ApoE4 carriers (Reiman et al, 2004;Scarmeas et al, 2003;Wierenga et al, 2013) or subjects with a family history of AD (Mosconi et al, 2014), have revealed alterations in glucose metabolism and CBF. Thus, a very early and causative effect might be possible.…”

Increased Hippocampal Blood Flow in Sedentary Older Adults at Genetic Risk for Alzheimer's Disease

“…Cerebrovascular dysregulation alters the brain’s control mechanisms that ensure nutrient delivery and control homeostasis for efficient brain functioning, [4] and there is evidence that cerebrovascular dysregulation is present in AD [5] and in individuals at genetic risk for developing AD [37, 38, 41]. Aerobic fitness has been found to improve cerebral hemodynamics (e.g., maximal oxygen consumption, middle cerebral artery velocity, cerebrovascular resistance/conductance) in older adult males [28], increase the change in vasodilator response to hypercapnia in older adults [62], and reduce age-related declines in CBF [23].…”

“…Genotyping for APOE alleles was performed using PCR Restriction Fragment Length Polymorphism analysis [For details, see 38, 41]. …”

Lack of Influence of Apolipoprotein E Status on Cognition or Brain Structure in Professional Fighters

“…[8][9][10] Briefly, genomic DNA was collected from blood DNA extracted using Qiamp DNA blood maxi kit (Qiagen) and APoE genotyping was performed using Applied Biosystems TaqMan SNP Genotyping Assay. The amplification reaction contained 5 lL genomic DNA, 2.5 U of Taq DNA Polymerase (New England Biolabs, Inc, Ipswich, MA), 1 · ThermoPol Reaction Buffer (New England Biolabs), 0.3 mmol/L deoxynucleotide (dNTPs), 10% dimethyl sulfoxide (DMSO), and 0.3 lmol/L of each primer (forward primer: 5¢-ACGCGGGCACGGCTGTCCAAGGA-3¢; reverse primer: 5¢-GCGGGCCCCGGCCTGGTACAC-3¢).…”