Researchers Identify Amyloid-β Pathology in Several Primary Progressive Aphasia Variants

Primary progressive aphasia (PPA) classification system suggests that age and apolipoprotein E genotype should be taken into account when interpreting β biomarkers in PPA.

According to study results published in the Annals of Neurology, patients with logopenic primary progressive aphasia (PPA) are more likely to have amyloid-β positivity and be diagnosed with Alzheimer disease compared with patients with non-fluent PPA or semantic PPA.

Individual data of patients with PPA from 36 centers were obtained (N=1251), with patients subdivided into logopenic PPA (n=443), non-fluent PPA (n=333), semantic PPA (n=401), and mixed/unclassifiable PPA (n=74) variants. All patients had amyloid-β pathology measured in cerebrospinal fluid (n=600), positron emission tomography (PET) (n=366), and/or autopsy (n=378). Generalized estimating equation models were used to estimate the prevalence of amyloid-positivity based on age, PPA variant, and apolipoprotein E (APOE) ε4 status.

A significantly greater percentage of patients with the logopenic PPA variant had amyloid-β positivity vs patients with non-fluent PPA or semantic PPA (86% vs 20% and 16%, respectively; P <.001). In patients with non-fluent PPA, the prevalence of amyloid-β positivity significantly increased from age 50 to 80 (10% vs 27%, respectively; P <.01). In addition, amyloid-β positivity prevalence increased in patients with semantic PPA from 6% at age 50 to 32% at age 80 (P <.001). No similar increases were observed in patients with logopenic PPA (P =.94).

Overall, APOE ε4 carriers were more likely to be amyloid-β-positive compared with non-carriers (58% vs 35%, respectively; P <.001). The most frequent pathologic diagnosis in patients with logopenic PPA was Alzheimerdisease based on autopsy data (76%).

In addition, frontotemporal lobar degeneration-TDP-43 and frontotemporal lobar degeneration-TDP-43/tau were the most frequently pathologic diagnoses in semantic PPA (80%) and non-fluent PPA 64%).

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Study limitations include its retrospective nature, as well as the variability in clinical work-up across centers, particularly with regard to neuropsychological assessment.

Future studies on the genetic features and structural/functional imaging of PPA may “improve accuracy of the PPA diagnosis and the identification of the underlying etiology, which will lead to more accurate and efficient participant inclusion in clinical trials with disease modifying agents tailored to reduce cerebral β tau and/or TDP-43 pathology.”


Bergeron D, Gorno-Tempini ML, Rabinovici GD, et al. Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. Ann Neurol. 2018;84(5):729-740.