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Amyloid and tau PET in sporadic early‐onset Alzheimer’s disease: Preliminary results from LEADS
Author(s) -
Rabinovici Gil D.,
Iaccarino Leonardo,
La Joie Renaud,
LesmanSegev Orit H.,
SoleimaniMeigooni David N.,
Provost Karine,
Collins Jessica A.,
Aisen Paul S.,
Borowski Bret J,
Eloyan Ani,
Fagan Anne,
Foroud Tatiana M.,
Gatsonis Constantine,
Jack Clifford R.,
Kramer Joel H.,
Saykin Andrew J.,
Toga Arthur W.,
Vemuri Prashanthi,
Day Gregory S.,
GraffRadford Neil R.,
Honig Lawrence S.,
Jones David T.,
Masdeu Joseph C.,
Mendez Mario F.,
Onyike Chiadi U.,
Rogalski Emily J.,
Salloway Stephen P.,
Wolk David A.,
Wingo Thomas S.,
Koeppe Robert A.,
Dickerson Brad C.,
Carrillo Maria C.,
Apostolova Liana G.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041613
Subject(s) - early onset alzheimer's disease , standardized uptake value , alzheimer's disease , amyloid (mycology) , medicine , psychology , nuclear medicine , pathology , disease , positron emission tomography
Background Previous studies have reported that age modifies the distribution and burden of tau (and, to a lesser extent, amyloid) pathology in sporadic Alzheimer’s disease (AD). Here we present preliminary baseline amyloid and tau PET results from the Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS), a multi‐site longitudinal study of sporadic early‐onset AD. Method 135 patients meeting clinical criteria for MCI or probable AD and 50 cognitively normal controls (all age<65 at enrollment) were enrolled at 12 US centers between August 2018 and December 2019 (Table 1). 18 F‐Florbetaben amyloid‐PET (FBB) was used to assign patients to EOAD (amyloid‐positive) or EOnonAD (amyloid‐negative) subgroups based on visual rating and semi‐quantification. 130 patients and all controls had 18 F‐Flortaucipir tau‐PET (FTP). Regional Standardized Uptake Value Ratios (SUVR) for FBB (whole cerebellum reference) and FTP (inferior cerebellar gray reference) were extracted using co‐registered 3T‐MRI. Result 98 patients (72.6%) were amyloid PET‐positive (EOAD) and 37 (27.4%) were amyloid PET‐negative (EOnonAD). Compared to EOAD, EOnonAD patients had higher MMSE, MOCA and CDR sum‐of‐boxes (CDR‐SB) and were more frequently male (Table 1). Patients with EOAD showed elevated FBB and FTP SUVR in temporoparietal and frontal cortex compared to CN and EOnonAD (Figures 1‐2). In EOAD, MMSE, MOCA and CDR‐SB were significantly correlated with FTP SUVR (Figure 3), while no significant correlations were found with FBB SUVR. EOnonAD patients showed variable FTP binding ranging from negative to mildly elevated binding in anterior temporal and frontal cortex and underlying white matter. Two EOnonAD cases showed intense FTP binding comparable to typical EOAD cases, despite visually and quantitatively negative FBB scans. Conclusion Patients with clinically mild, sporadic EOAD typically show an extensive distribution and burden of tau pathology in the setting of positive amyloid PET. Global clinical measures correlate with tau but not amyloid PET. Over 25% of patients meeting clinical criteria for early‐onset MCI/probable AD have negative amyloid PET, suggesting alternative etiologies for cognitive decline. These findings will inform future design of drug trials in this important and under‐studied population.