Clinical Manifestations

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Logopenic primary progressive aphasia (lvPPA) is an atypical Alzheimer's disease (AD) presentation.
• Non-fluent/agrammatic PPA (nfvPPA) is typically linked to frontotemporal lobar degeneration (FTLD).
• Annexin A11 (ANXA11) gene mutations, usually associated with FTLD/ALS, are rarely reported in semantic PPA (svPPA).

Purpose of the Study:

• To report the clinical, genetic, and imaging findings of a unique case of atypical AD.
• To describe a patient with a mixed lvPPA/nfvPPA phenotype and an ANXA11 gene mutation.

Main Methods:

• Case report of a 65-year-old woman with progressive language impairment.
• Clinical assessment including Mini-Mental State Examination (MMSE), semantic verbal fluency, and Boston Naming Test.
• Cerebrospinal fluid (CSF) analysis for AD biomarkers (tau, Aβ).
• Genetic testing for ANXA11 gene mutation.
• Magnetic Resonance Imaging (MRI) and Diffusion Tensor Tractography (DTI) for white matter (WM) tract analysis.

Main Results:

• The patient presented with word-finding difficulties, sentence repetition issues, naming deficits, memory problems, effortful speech, and agrammatism over 8 years.
• CSF analysis indicated AD pathology (elevated t-tau/p-tau, decreased Aβ 42/40).
• Genetic testing confirmed an ANXA11 gene mutation.
• MRI showed left-predominant frontoinsular and perisylvian/temporoparietal atrophy.
• DTI revealed widespread left-hemisphere WM atrophy in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF), predominantly in ILF and SLF.

Conclusions:

• This case highlights the importance of considering AD in atypical PPA presentations, even with mixed phenotypes.
• It underscores the clinical variability associated with ANXA11 gene mutations.
• Diffusion tensor tractography (DTI) is crucial for identifying specific white matter (WM) patterns in different PPA subtypes.