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Parent’s age at onset may help predict Alzheimer’s disease biomarker levels

Asymptomatic people with a family history of sporadic Alzheimer’s disease were more likely to show abnormal cerebrospinal fluid and brain amyloid- biomarkers as they neared their parent’s onset age, indicating that proximity to parental symptom onset may help predict amyloid- biomarker changes, according to study findings.

“The best time window to prevent [Alzheimer’s disease] is likely when individuals are still asymptomatic, before extensive neuronal degeneration has occurred. Identifying asymptomatic individuals is challenging and expensive, posing significant difficulties for the current generation of clinical trials,” Sylvia Villeneuve, PhD, department of psychiatry, McGill University, and Douglas Mental Health University Institute, Montreal, and colleagues wrote. “In autosomal dominant [Alzheimer’s disease], symptom onset is determinable across generations. Whether the parent’s age at onset can help determine biomarker abnormalities in [Alzheimer’s disease] is not known.”

Researchers examined whether calculating sporadic parental estimated years to symptom onset could shed light on amyloid- levels in asymptomatic people with parental history of Alzheimer’s disease dementia. They further examined whether the heterogeneity of Alzheimer’s disease, apolipoprotein E 4 (APOE4) and female sex affects the link between sporadic parental estimated years to symptom onset score and amyloid- levels.

In their study, the investigators analyzed amyloid-1-42 in cerebrospinal fluid (CSF) specimens from 101 cognitively unimpaired individuals enrolled in the Presymptomatic Evaluation of Novel or Experimental Treatments for Alzheimer Disease (PREVENT-AD) cohort. They estimated each participant’s closeness to their parent’s symptom onset by subtracting their relative’s onset age from their current age. Using CSF and Pittsburgh compound B carbon 11–labeled positron emission tomography (PIB-PET) amyloid- biomarkers, they performed analyses again in the Adult Children Study (ACS) and Wisconsin Registry for Alzheimer Prevention (WRAP) cohorts.

Along with a subset of the 101 PREVENT-AD participants, analysis included 128 ACS participants (112 of whom underwent CSF measurement and 107 of whom underwent PIB-PET) and 135 WRAP participants (85 of whom underwent CSF measurement and all of whom underwent PIB-PET).

The results showed that PREVENT-AD participants nearing their parent’s Alzheimer’s disease onset age had lower CSF amyloid-1-42 levels (P = .04); this relationship was stronger in APOE4 carriers (P = .03) and women (P = .02). Among ACS participants, the researchers observed the same association using PIB-PET data, and using CSF and PIB-PET data also replicated the female sex interaction. Although the findings were not replicated using cross-sectional data among WRAP participants, the link between parent’s Alzheimer’s disease onset age and CSF amyloid- levels and the APOE interaction were replicated using PIB-PET longitudinal data.

“Our finding of an association between proximity to parental symptom onset and amyloid- in three independent cohorts at approximately 50 to 70 years of age supports the well-accepted idea that brain changes start many years before clinical symptoms,” Villeneuve and colleagues wrote. “Overall, the sporadic parental [estimated years to symptom onset] score may help the identification of asymptomatic candidates for clinical trials.” – by Savannah Demko

Disclosures: Villeneuve reports having a Canada research chair and support from the Alzheimer’s Association, Alzheimer’s Society of Canada, Brain Canada Foundation and Canadian Institutes of Health Research. Please see the full study for other authors’ relevant financial disclosures.