The study by Honea and colleagues adds very nicely to an increasing body of literature showing that having a maternal history of Alzheimer's disease (AD) is a major risk factor for developing AD among normal individuals. In a series of brain imaging papers starting back in 2007, we showed that adult children of AD-affected mothers have progressively reduced brain glucose metabolism and increased amyloid-β pathology consistent with AD, as compared to demographically matched individuals with AD fathers and those with no parents affected. The study by Honea et al. shows that normal elderly with AD mothers also show higher rates of atrophy (reflecting neuronal loss) on MRI over a two-year window.

These findings are very important because 1) increased brain atrophy rates are known to be strongly associated with future decline from normal cognition to AD; 2) they provide evidence from structural, besides functional and pathological, deficits in individuals with AD mothers; 3) MRI is widely available for clinical practice as well as clinical trials, and is non-invasive and...  Read more

The study by Honea and colleagues adds very nicely to an increasing body of literature showing that having a maternal history of Alzheimer's disease (AD) is a major risk factor for developing AD among normal individuals. In a series of brain imaging papers starting back in 2007, we showed that adult children of AD-affected mothers have progressively reduced brain glucose metabolism and increased amyloid-β pathology consistent with AD, as compared to demographically matched individuals with AD fathers and those with no parents affected. The study by Honea et al. shows that normal elderly with AD mothers also show higher rates of atrophy (reflecting neuronal loss) on MRI over a two-year window.

These findings are very important because 1) increased brain atrophy rates are known to be strongly associated with future decline from normal cognition to AD; 2) they provide evidence from structural, besides functional and pathological, deficits in individuals with AD mothers; 3) MRI is widely available for clinical practice as well as clinical trials, and is non-invasive and affordable; and 4) together with previous studies, these new findings strengthen the hypothesis of a genetic component to the biomarker abnormalities in this group of at-risk individuals.

The genetics of late-onset AD are still elusive, but it seems clear that late-onset AD is a complex and possibly multifactorial disease where many different risk factors play a role. It is becoming clear that genes involved with maternal transmission lead the offspring to develop an AD-biological phenotype around middle age. Among other possibilities, mitochondrial DNA is entirely maternally inherited in humans and may very well be associated with the imaging findings.

Additionally, these findings are consistent with epidemiological studies showing that maternal transmission of AD is more frequent than paternal transmission, and is associated with greater risk and poorer cognitive performance in the offspring. We published a review chapter that summarizes these data (Mosconi et al., 2010).

More studies with larger samples and longer follow-ups are needed to follow individuals with AD mothers (and fathers) until some of them actually develop AD in order to determine the prediction accuracy and absolute risk of MRI-determined atrophy and other biomarkers for AD.

References:
Mosconi L, Berti V, Swerdlow RH, Pupi A, Duara R, de Leon M. Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes. Hum Genomics. 2010 Feb;4(3):170-93. Abstract

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