Study: Family history has greater role in Alzheimers than previously thought
Family history of Alzheimer disease (AD) is associated with several age-related changes that appear to influence AD biomarker abnormalities beyond the increased risk of the APOE4 gene, according to a report published in the October issue of Archives of Neurology. Previously, researchers suspected that AD has a lengthy preclinical period prior to the development of symptoms, in which cerebral lesions accumulate.
The Antecedent Biomarkers for AD: The Adult Children Study (ACS), which is focused on a cohort of 269 cognitively normal 43- to 76-year-old individuals, has examined multiple biomarkers for AD before its symptomatic stages. These include MRI-based brain volumes, diffusion tensor imaging-based measures of white matter microstructure, cerebrospinal fluid (CSF) and PET data using the Pittsburgh compound B (PIB).
Chengjie Xiong, PhD, from Washington University School of Medicine, St. Louis, and colleagues designed the current study to assess whether familial history alone is associated with AD risk beyond that of the E4 allele of apolipoprotein E (APOE4).
“Age-adjusted cerebrospinal fluid AB42 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 reported. “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 wrote, “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 AB42 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,” according to Xiong and colleagues.
The researchers concluded, “Changes in CSF and PIB biomarkers have the potential to capture the earliest possible antecedent events.” These biomarkers could indicate the onset of AD prior to observable cognitive decline.
The Antecedent Biomarkers for AD: The Adult Children Study (ACS), which is focused on a cohort of 269 cognitively normal 43- to 76-year-old individuals, has examined multiple biomarkers for AD before its symptomatic stages. These include MRI-based brain volumes, diffusion tensor imaging-based measures of white matter microstructure, cerebrospinal fluid (CSF) and PET data using the Pittsburgh compound B (PIB).
Chengjie Xiong, PhD, from Washington University School of Medicine, St. Louis, and colleagues designed the current study to assess whether familial history alone is associated with AD risk beyond that of the E4 allele of apolipoprotein E (APOE4).
“Age-adjusted cerebrospinal fluid AB42 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 reported. “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 wrote, “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 AB42 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,” according to Xiong and colleagues.
The researchers concluded, “Changes in CSF and PIB biomarkers have the potential to capture the earliest possible antecedent events.” These biomarkers could indicate the onset of AD prior to observable cognitive decline.