Cross‐sectional and longitudinal comparisons of biomarkers and cognition among asymptomatic middle‐aged individuals with a parental history of either autosomal dominant or late‐onset Alzheimer's disease

• Published in: Alzheimer's & dementia Vol. 19; no. 7; pp. 2923 - 2932
• Main Authors: Xiong, Chengjie, McCue, Lena M., Buckles, Virginia, Grant, Elizabeth, Agboola, Folasade, Coble, Dean, Bateman, Randall J., Fagan, Anne M, Benzinger, Tammie L. S., Hassenstab, Jason, Schindler, Suzanne E., McDade, Eric, Moulder, Krista, Gordon, Brian A., Cruchaga, Carlos, Day, Gregory S., Ikeuchi, Takeshi, Suzuki, Kazushi, Allegri, Ricardo F., Vöglein, Jonathan, Levin, Johannes, Morris, John C.
• Format: Journal Article
• Language: English
• Published: United States 01.07.2023
• Subjects: Adult; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer's disease (AD); Amyloid beta-Peptides - cerebrospinal fluid; autosomal dominant Alzheimer's disease (ADAD), cerebrospinal fluid (CSF); Biomarkers - cerebrospinal fluid; Cognition; Cross-Sectional Studies; Humans; magnetic resonance imaging (MRI); Middle Aged; Parents; Pittsburgh compound‐B (PiB); positron emission tomography (PET); Positron-Emission Tomography; magnetic resonance imaging (MRI); Alzheimer's disease (AD); Pittsburgh compound-B (PiB); autosomal dominant Alzheimer's disease (ADAD), cerebrospinal fluid (CSF); positron emission tomography (PET)
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.12912

Background Comparisons of late‐onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD) are confounded by age. Methods We compared biomarkers from cerebrospinal fluid (CSF), magnetic resonance imaging, and amyloid imaging with Pittsburgh Compound‐B (PiB) across four groups of 387 cognitively normal participants, 42 to 65 years of age, in the Dominantly Inherited Alzheimer Network (DIAN) and the Adult Children Study (ACS) of LOAD: DIAN mutation carriers (MCs) and non‐carriers (NON‐MCs), and ACS participants with a positive (FH+) and negative (FH–) family history of LOAD. Results At baseline, MCs had the lowest age‐adjusted level of CSF Aβ42 and the highest levels of total and phosphorylated tau‐181, and PiB uptake. Longitudinally, MC had similar increase in PiB uptake to FH+, but drastically faster decline in hippocampal volume than others, and was the only group showing cognitive decline. Discussion Preclinical ADAD and LOAD share many biomarker signatures, but cross‐sectional and longitudinal differences may exist.