Cerebrospinal Fluid Biomarkers as a Diagnostic Tool of the Underlying Pathology of Primary Progressive Aphasia

Objective This study aimed to determine the most appropriate cognitive and cerebrospinal fluid (CSF) biomarker setting to distinguish frontotemporal dementia (FTD) from Alzheimer’s disease (AD). Method Patients with FTD, those with AD, and those without dementia were enrolled in this study. CSF amyloid-ß 42 (Aß42), total (t)-tau, and phosphorylated (p)-tau concentrations were determined by enzyme-linked immunosorbent assays. Cognition was evaluated by the Mini-Mental State Examination (MMSE) and its domain scores. The associations of CSF biomarkers with cognitive measures were examined using regression models and the diagnostic value of CSF biomarkers was determined by receiver operating characteristics curves. Results CSF Aß42 levels were lower, whereas t-tau/Aß42 and p-tau/Aß42 ratios were higher in patients with AD compared with those with FTD. Some MMSE domain scores were different in FTD and AD, but they did not improve the ability to distinguish between the two pathologies. Poor temporal orientation scores were associated with low Aß42 levels only in patients with FTD. The p-tau/Aß42 ratio reached sufficient levels of sensitivity and specificity to discriminate FTD with primary progressive aphasia from AD. Conclusions The ratio of CSF p-tau/Aß42 is a sensitive and specific biomarker for discriminating patients with primary progressive aphasia from those with AD.

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Cortical developmental abnormalities in logopenic variant primary progressive aphasia with dyslexia

Brain Communications ◽

10.1093/braincomms/fcz027 ◽

2019 ◽

Vol 1 (1) ◽

Author(s):

Zachary A Miller ◽

Salvatore Spina ◽

Mikhail Pakvasa ◽

Lynne Rosenberg ◽

Christa Watson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Age Of Onset ◽

Primary Progressive Aphasia ◽

Later Life ◽

Brain Regions ◽

Developmental Abnormalities ◽

Progressive Aphasia ◽

Primary Progressive ◽

Underlying Pathology

Abstract An increased prevalence of dyslexia has been observed in individuals diagnosed with primary progressive aphasia, most notably the logopenic variant primary progressive aphasia. The underlying pathology most commonly associated with logopenic variant primary progressive aphasia is Alzheimer’s disease. In this clinical case report series, we describe the neuropathological findings of three patients with logopenic variant primary progressive aphasia and developmental dyslexia, each demonstrating a pattern of cerebrocortical microdysgenesis, reminiscent of findings first reported in dyslexic individuals, alongside expected Alzheimer’s disease pathology. Neurodevelopmental and most severe Alzheimer’s disease pathological changes overlapped within perisylvian brain regions, areas associated with phonological deficits in both logopenic variant primary progressive aphasia and dyslexia. These three cases with pathological findings support the hypothesis that early-life neurodevelopmental changes might influence later-life susceptibility to neurodegenerative disease and could contribute to non-amnestic, early age-of-onset presentations of Alzheimer’s disease. Larger studies investigating neurobiological vulnerability across the lifespan are needed.

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