Exploring the basis of phenotypic diversity in Alzheimer's disease.

BACKGROUND: Alzheimer's Disease (AD) is the most common type of dementia and affects more than 50 million people around the world. Although there is no effective treatment for the disease at the moment, early detection is still critical to start an early management plan and try out various interventions. Besides the stereotypical Amnestic Syndrome, many atypical pehnotypes exist which make accurate early diagnosis challenging.

METHOD: Examined Corticobasal Syndrome (CBS), behavioural variant of Frontotemporal Dementia (bvFTD), Posterior Cortical Atrophy (PCA), and Primary Progressive Aphasia (PPA) cases correlating with AD's onset. As such, this literature review investigated the reasons underpinning the selective regional vulnerability leading to clinical diversity in AD.

RESULT: The majority of AD is sporadic, caused by phosphorylated-tau aggregates and amyloid-β depositions in neurons or extracellular space. Increasing age is the dominant risk factor for AD development and the major genetic risk factor for sporadic AD is ApoE4. A small proportion of AD is familial, due to mutations in APP, PSEN1, and PSEN2 genes. The available research findings suggest that diverse clinical presentations correlated with selective degeneration and pathology development in different brain regions. The different regions with originally pathological alternations of each phenotype may help explain the conundrum of polytropic presentations, that primary motor cortex is significantly affected in CBS, basal ganglia in bvFTD, posterior part of the brain in PCA, and temporoparietal areas in PPA. Research indicates that the presence of ApoE4 is significant for the development of all AD phenotypes. In addition, while some studies reported several famial cases, these are not typically thought to be representative and thus more studies are needed.

CONCLUSION: The diverse clinical phenotypes of AD, including AS, CBS, bvFTD, PCA, and PPA, share similar pathogenesis and genetic factors, but each phenotype has divergent patterns of regional distribution of the pathology.