Levels of Spinal Fluid Amyloid Become Abnormal Long Before Alzheimer Disease Is Clinically Apparent

Levels of both amyloid-β₄₂ (Aβ₄₂) and tau proteins likely play a central role in the pathogenesis of Alzheimer disease (AD). However, initial studies using monoclonal antibodies to target Aβ₄₂ were unsuccessful in slowing the disease. This led some experts to call for abandoning anti-amyloid therapy, whereas others argued for earlier anti-amyloid treatment, which has produced modest benefits (NEJM JW Gen Med Feb 15 2023 and N Engl J Med 2023; 388:9).

In a new study from China, researchers enrolled cognitively normal people (age range, 45–65) and followed them for 20 years, performing repeated cognitive assessments, brain imaging, and spinal fluid collection and testing. Data from the 648 who developed AD were compared with a matched group of…