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Confirmed: Amyloid, Tau Levels Rise Years Before Alzheimer’s Onset
A new study supports the hypothesis that changes in levels of amyloid and tau occur many years before the emergence of clinical symptoms of Alzheimer’s disease (AD).
“Our results confirm accelerated biomarker changes during preclinical AD and highlight the important role of amyloid levels in tau accelerations,” the investigators note.
“These data may suggest that there is a short therapeutic window for slowing AD pathogenesis prior to the emergence of clinical symptoms ― and that this window may occur after amyloid accumulation begins, but before amyloid has substantial impacts on tau accumulation,” study investigator Corinne Pettigrew, PhD, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News.
The study was published online November 18 in Alzheimer’s and Dementia.
Clear Impact of APOE4
The findings also suggest that among APOE4 carriers, amyloid onset occurs at an earlier age and rates of amyloid positivity are higher, but there are no differences in rates of change in amyloid over time.
“APOE4 genetic status was not related to changes in CSF beta-amyloid after accounting for the fact that APOE4 carriers have higher rates of amyloid positivity,” said Pettigrew.
“These findings suggest that APOE4 genetic status shifts the age of onset of amyloid accumulation (with APOE4 carriers having an earlier age of onset compared to non-carriers), but that APOE4 is not related to rates of change in CSF beta-amyloid over time,” she added.
“Thus, cognitively normal APOE4 carriers may be in more advanced preclinical AD stages at younger ages than individuals who are not APOE4 carriers, which is likely relevant for optimizing clinical trial recruitment strategies,” she said.
Alzheimers Dement. Published online November 18, 2022. Full text
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