Cognitively normal individuals with AD parents may be at risk for developing aging-related cortical thinning patterns characteristic of AD

Abstract

Children of Alzheimer's Disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p < 0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female.

Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers

“…Twentytwo of the 24 APOE4 noncarriers are ε3/ε3 homozygotes and two are ε2/ε3 heterozygotes. The proportion of ε4 carriers in our study is higher than the general population, but is in line with the similar studies published recently (Caselli et al, 2011; Reiter et al, 2012). …”

Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD

“…These data are consistent with epidemiologic and biomarker findings that maternal transmission is associated with higher risk than paternal transmission, independent of increased female longevity. 2,11,[13][14][15][16][17][18][26][27][28][29][30][31] Present findings expand on prior unimodality biomarker studies showing multiple biomarker deficits in NL FHm, which appeared to be overall less severe than in FHmp. Interestingly, NL FHm was the only group in which Ab load did not significantly exceed hypometabolism.…”

“…It remains to be established whether Ab accumulation is also an early event in LOAD. 1 Previous brain imaging studies have shown that, among NL individuals who have parents with LOAD, those with maternal FH (FHm) present with increased Ab load on 11 C-Pittsburgh compound B (PiB)-PET, 11,12 progressive glucose metabolism reductions on 18 F-fluoro-2-deoxyglucose (FDG)-PET, 13,14 and gray matter volume (GMV) loss on MRI [15][16][17][18] in the same regions as those with clinical AD. In contrast, NL individuals with paternal FH (FHp) are far less likely to show biomarker abnormalities.…”

“…In contrast, NL individuals with paternal FH (FHp) are far less likely to show biomarker abnormalities. 11,[13][14][15][16][17][18] There are no biomarker studies that examined NL individuals with maternal and paternal FH (FHmp).…”

The Alzheimer's disease mitochondrial cascade hypothesis: Progress and perspectives

“…As mentioned above maternal inheritance also influences memory test performance in middle-aged individuals, since in some demographics individuals with AD mothers do not score as well on memory tests as individuals with AD fathers [117]. A growing number of databases using different approaches currently report maternal inheritance-associated AD endophenotypes [138-141]. …”