The bivariate distribution of amyloid- β and tau: relationship with established neurocognitive clinical syndromes

We examined these clinical groups in relation to the bivariate distribution of amyloid and tau PET values. Individuals were grouped into amyloid (A)/tau (T) quadrants based on previously established abnormality cut points of s tandardized uptake value ratio 1.48 (A) and 1.33 (T). Individual participants largely fell into one of three amyloid/tau quadrants: low amyloid and low tau (A−T−), high amyloid and low tau (A+T−), or high amyloid and high tau (A+T+). Seventy per cent of cognitively unimpaired and 74% of FTD pa rticipants fell into the A−T− quadrant. Participants with mild cognitive impairment spanned the A−T− (42%), A+T− (28%), and A+T+ (27%) quadrants. Probable dementia with Lewy body participants spanned the A−T− (38%) and A+T− (44%) quadrants. Most (89%) participants with Alzheimer clin ical syndrome fell into the A+T+ quadrant. These data support several conclusions. First, among 1343 participants, abnormal tau PET rarely occurred in the absence of abnormal amyloid PET, but the reverse was common. Thus, with rare exceptions, amyloidosis appears to be required for high levels of 3R /4R tau deposition. Second, abnormal amyloid PET is compatible with normal cognition but highly abnormal tau PET is not. These two conclusions support a dynamic biomarker model in which Alzheimer’s disease is characterized first by the appearance of amyloidosis and later by tauopathy, with tauopat hy being the proteinopathy associated with clinical symptoms. Third, ...
Source: Brain - Category: Neurology Source Type: research