Family history of Alzheimer disease is associated with several age-related changes that appear to influence Alzheimer disease (AD) biomarker abnormalities beyond the increased risk of the APOE4 gene, according to a report published in the October issue of Archives of Neurology, one of the JAMA/Archives journals.

According to background information in the article, the "recent advances suggest that Alzheimer disease (AD) has a lengthy period in which cerebral lesions gradually accumulate in the absence of symptoms, eventually causing sufficient synaptic and neuronal damage to result in symptomatic AD. Since 2005, Antecedent Biomarkers for AD: The Adult Children Study (ACS) has enrolled a cohort of cognitively normal 43 -- to 76-year-old individuals in an extensive study of biomarkers for AD before it symptomatic stages."

Chengjie Xiong, Ph.D., from Washington University School of Medicine, St. Louis, and colleagues assessed whether family history alone is associated with AD risk beyond that of the ε4 allele of apolipoprotein E (APOE4), a genetic biomarker indicating higher risk for susceptibility for AD. A total of 269 cognitively normal middle-to older-age individuals with and without a family history of Alzheimer disease participated in the study. A family history was identified as having at least one biological parent with age at onset for dementia of the Alzheimer type (DAT) of less than 80 years, and a negative family history was defined as both biological parents living to age 70 or longer without DAT. The participants underwent clinical and cognitive measures, including magnetic resonance imaging-based brain volumes, cerebrospinal fluid biomarkers (CSF; collected by lumbar puncture), and positron emission tomography using the [11C] benzothiazole tracer, Pittsburgh compound B [PET PIB].

"Age-adjusted cerebrospinal fluid Aβ42 was decreased for individuals with APOE4 compared with the level for those without, and the decrease was larger for individuals with a positive family history compared with the decrease for those without," the authors report. "For individuals younger than 55, an age-related increase in mean cortical binding potential was associated with APOE4 but not family history. For individuals older than 55, a positive family history and a positive APOE4 implied the fastest age-related increase in mean cortical binding potential." The authors add, "the current results point to the likelihood of non-APOE susceptibility genes for AD..."

." ..among cognitively normal middle- to older-aged individuals, age-related changes in brain Aβ42 metabolism as well as local microstructural characteristics of water diffusion in certain brain regions are influenced by family history of AD, suggesting that they are likely early events in AD pathogenesis," the authors write. "Whereas cognitive changes might be later events in the neurodegenerative sequence before the onset of DAT, changes in CSF and PIB biomarkers have the potential to capture the earliest possible antecedent events," the authors conclude.