ABSTRACT
Parental lineage has been shown to increase the risk of Alzheimer's disease (AD) in the offspring, with greater risk attributed to maternal lineage. While 40 genes/loci have been linked to the risk of developing AD, none has been found on the X chromosome. We propose a new method to estimate the risk for developing AD mediated by the X chromosome in a subgroup of late-onset AD (LOAD) patients with amnestic mild cognitive impairment (aMCI) or early AD and unilateral ancestral history of AD or dementia, and pilot-test it on our clinic data. Records of patients aged 55-80 years presenting to our Memory Disorders Clinic with aMCI or early AD between May 2015 and September 2020, were reviewed, counting patients with a family history of AD or dementia and unilateral ancestral lineage. The X chromosome-attributable relative risk was estimated by calculating the following odds ratio (OR): (women with paternal lineage:women with maternal lineage)/(men with paternal lineage:men with maternal lineage). The proportion of genetic risk borne by the X chromosome is equal to (OR-1)/OR. 40 women aged 66.1 ± 5.1 years (mean ± standard deviation) and 31 men aged 68.1 ± 6.5 were identified. The OR was (18:22)/(6:25) = 3.4 (95% confidence interval 1.1-10.1; p = 0.027). The estimated proportion of genetic risk borne by the X chromosome in this population is 70% (95% CI 12-90%). This paper presents the first application of a new method. The numbers are small, the confidence intervals wide. The findings need to be replicated. The method may be generalizable to other diseases.
