Alzheimer mimicry: LATE and PART

Area of Science:

• Neurology
• Geriatrics
• Biomarker Research

Background:

• Alzheimer's disease (AD) is the leading cause of dementia in individuals over 75, characterized by progressive cognitive decline.
• Accurate classification of AD and non-AD cases is essential for understanding disease mechanisms and developing treatments.
• Current diagnostic methods, including neuroimaging and CSF biomarkers, aid AD diagnosis but face challenges in differentiating it from other age-related pathologies.

Purpose of the Study:

• To highlight the diagnostic challenges in differentiating Alzheimer's disease (AD) from non-AD pathologies.
• To discuss the role of biomarkers in identifying conditions like suspected non-Alzheimer disease pathophysiology (SNAP).
• To emphasize the need for improved diagnostic tools for accurate diagnosis and treatment in elderly patients with cognitive impairment.

Main Methods:

• Review of current diagnostic approaches for Alzheimer's disease, including structural, functional, and molecular brain imaging.
• Analysis of cerebrospinal fluid (CSF) biomarkers for amyloid pathology and neurodegeneration.
• Inclusion of APOE genotype as a diagnostic support.
• Discussion of clinical presentations and progression of non-AD pathologies like SNAP, PART, and LATE.

Main Results:

• Biomarker utilization aids in identifying individuals with mild cognitive impairment who are amyloid-negative, termed suspected non-Alzheimer disease pathophysiology (SNAP).
• SNAP and other non-AD pathologies (Argyrophilic Grain Disease, Tangle Predominant Dementia, TDP-43 proteinopathy, PART, LATE) can mimic AD, causing diagnostic uncertainty in up to 30% of cases.
• Existing diagnostic tools are insufficient for fully characterizing the complexities of these conditions, leading to potential misdiagnoses.

Conclusions:

• Accurate differentiation between AD and non-AD pathologies is critical for effective patient management.
• Limitations in current diagnostic tools necessitate further research and development for precise diagnosis of dementia subtypes.
• Addressing diagnostic ambiguities is crucial for reducing misdiagnoses and implementing appropriate therapeutic strategies for elderly patients with cognitive impairment.