Amyloid and Tau PET Positivity in Progressive Agrammatic Aphasia and Apraxia of Speech

Article type: Research Article

Authors: Tetzloff, Katerina A.^{a; *} | Duffy, Joseph R.^a | Clark, Heather M.^a | Pham, Nha Trang Thu^b | Machulda, Mary M.^c | Botha, Hugo^a | Jack Jr., Clifford R.^b | Dickson, Dennis W.^b | Lowe, Val J.^b | Josephs, Keith A.^a | Whitwell, Jennifer L.^b | Utianski, Rene L.^a

Affiliations: [a] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [b] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [c] Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA

Correspondence: [*] Correspondence to: Katerina A. Tetzloff, PhD, 200 1^st Street SW, Rochester, MN 55905, USA. Tel.: +1 507 990 0207; E-mail: tetzloff.katerina@mayo.edu.

Abstract: Background:The agrammatic variant of primary progressive aphasia (PAA), primary progressive apraxia of speech (PPAOS), or a combination of both (AOS-PAA) are neurodegenerative disorders characterized by speech-language impairments and together compose the AOS-PAA spectrum disorders. These patients typically have an underlying 4-repeat tauopathy, although they sometimes show evidence of amyloid-β and tau deposition on PET, suggesting Alzheimer’s disease (AD). Given the growing number of pharmacologic treatment options for AD, it is important to better understand the incidence of AD pathology in these patients. Objective:This study aimed to evaluate the frequency of amyloid-β and tau positivity in AOS-PAA spectrum disorders. Sixty-five patients with AOS-PAA underwent a clinical speech-language battery and PiB PET and flortaucipir PET imaging. Methods:Global PiB PET standardized uptake value ratios (SUVRs) and flortaucipir PET SUVRs from the temporal meta region of interest were compared between patient groups. For 19 patients who had died and undergone autopsy, their PET and pathology findings were also compared. Results:The results showed that although roughly half of the patients are positive for at least one biomarker, their clinical symptoms and biomarker status were not related, suggesting that AD is not the primary cause of their neurodegeneration. All but one patient in the autopsy subset had a Braak stage of IV or less, despite four being positive on tau PET imaging. Conclusions:Inclusion criteria for clinical trials should specify clinical presentation or adjust the evaluation of such treatments to be specific to disease diagnosis beyond the presence of certain imaging biomarkers.

Keywords: Alzheimer’s disease, biomarkers, amyloid-β protein, tau protein

DOI: 10.3233/JAD-230912

Journal: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1759-1765, 2023