Basic Science and Pathogenesis.

Area of Science:

• Neurodegenerative Diseases
• Neuropathology
• Clinical Neurology

Background:

• Amyotrophic Lateral Sclerosis with Frontotemporal Dementia (ALS-FTD) presents with motor and cognitive impairments.
• TDP-43 proteinopathy is the hallmark, but diverse FTLD-TDP subtypes complicate diagnosis.
• This report focuses on a 69-year-old female diagnosed with ALS-FTD.

Purpose of the Study:

• To present an atypical case of ALS-FTD.
• To describe the clinical, cognitive, and pathological features.
• To highlight diagnostic and classification challenges.

Main Methods:

• A 69-year-old female with cognitive decline, dysarthria, and behavioral changes was evaluated.
• Neuropsychological testing and MRI were performed over time.
• Postmortem neuropathology and immunohistochemical analysis were conducted.

Main Results:

• The patient initially showed mild cognitive impairment (MCI) with visuospatial deficits, later progressing to ALS-FTD.
• Postmortem findings revealed mixed FTLD-TDP Type A and B pathology, mild cerebrovascular disease, and intermediate Alzheimer's disease neuropathological changes.
• TDP-43 inclusions were observed in the spinal cord and brain; possible C9ORF72 expansion was indicated.

Conclusions:

• This ALS-FTD case was atypical due to the absence of delusions and early visuospatial deficits.
• The mixed FTLD-TDP Type A+B pathology, usually linked to C9ORF72 expansions and delusions, further underscores its unusual nature.
• This case emphasizes the variability in ALS-FTD presentation and pathology.