Amyloid ‘Tipping Point’ Correlated to Onset of Alzheimer’s Symptom Onset

Research conducted by a team at Washington University in St. Louis, MO, using PET,  identified a ‘tipping point’ in amyloid accumulation where cognitively normal patients begin to experience the symptoms of sporadic Alzheimer’s disease. The study was published September 9, 2021, in Neurology.

“Brain amyloid burden was measured by amyloid PET with Pittsburgh compound B. The mean cortical standardized uptake value ratio (SUVR) was transformed into a timescale using longitudinal data. … A tipping point in amyloid accumulation was identified at a low level of amyloid burden (SUVR 1.2), after which nearly all individuals accumulated amyloid at a relatively consistent rate until reaching a high level of amyloid burden (SUVR 3.0). The average time between levels of amyloid burden was used to estimate the age at which an individual reached SUVR 1.2. Longitudinal clinical diagnoses for 180 individuals were aligned by the estimated age at SUVR 1.2. In the twenty-two individuals who progressed from cognitively normal to a typical AD dementia syndrome, the estimated age at which an individual reached SUVR 1.2 predicted the age at symptom onset,” wrote the team.

The authors concluded, “The age of symptom onset in sporadic AD is strongly correlated with the age that an individual reaches a tipping point in amyloid accumulation.”

According to AuntMinnie, lead author Schindler wrote, “The study’s clinical significance may apply when doctors are discussing positive Alzheimer’s disease test results with cognitively normal patients.”


Suzanne Schindler, Yan Li, Virginia D. Buckles, Brian Andrew Gordon, Tammie L.S. Benzinger, Guoqiao Wang, Dean Coble, William E. Klunk, Anne M. Fagan, David Holtzman, Randall J. Bateman, John C Morris, Chengjie Xiong. Predicting Symptom Onset in Sporadic Alzheimer Disease With Amyloid PET. Neurology Sep 2021, 10.1212/WNL.0000000000012775; DOI: 10.1212/WNL.0000000000012775 Accessed September 27, 2021, at

PET identifies ‘tipping point’ for patients with Alzheimer’s. September 17, 2021. Accessed September 27, 2021, at

Optional Caption Here