Investigation of phenotype-genotype correlation in APP, PSEN1 and PSEN2 in early onset Alzheimer's patients

Alzheimer's Disease (AD) is a neurodegenerative disease leading to synapses and neuron losses on various parts of central nervous system (CNS) and characterised by deficiency on cognitive functions, a number of neuropsychiatric and behavioral disorders. As the most frequent type of dementia, AD constitutes 60-80 percent of all dementia cases. Depending on age disease onset, it is defined as Early Onset Alzheimer's Disease (EOAD) for cases occuring under the age of 65 and Late Onset Alzheimer's Disease (LOAD) for cases seen above the age of 65. While EOAD contitutes 1-5 percent of Alzheimer cases, LOAD accounts for approximately 95 percent of the cases. Early onset autosomal dominant Alzheimer's Disease constitutes 5-10 percent of early onset Alzheimer's disease and approximately 1 percent of all patients. AD holds a complex genetic structure. It describes four locuses estimated as being in genetic infrastructure of AD. Three different genes are set as mutants for familial AD with an autosomal dominant inheritance pattern resulting in EOAD. These help to explain genetic risk of the disease: three genes described as amyloid precursor protein (APP) on chromosome 21, presenilin 1 (PSEN1) on chromosome 14 and presenilin 2 (PSEN2) on chromosome 1; with frequency %10-15, %30-70 and fewer than %5 respectively. The first genetic risk found for LOAD is an ε4 polymorphism of APOE gene (APOE4). Although a large number of risk genes are set after numerous genome-wide association studies in AD, none of them come up to the risk level performed by APOE4. In this study, we retrospectively analysed genotypic and phenotypic data (APP, PSEN1 and PSEN2 sequencing analyses; MMSE, Blessed and Instrumental Activities of Daily Living (IADL) scores) from all individuals with EOAD and to determine the differences between prognoses. We compared MMSE, Blessed and IADL test scores within patients. We found that the patients that who carrier for PSEN1 or PSEN2 genes developed Alzheimer's disease earlier than non-carriers (p:0.038). Due to low number of patients and lack of patients information, we could not analyse the differences between prognosis of the two groups. Previously, there is a study about the relationship between APOE gene polymorphisms and lipid profiles in Alzheimer patients (1), and to our knowledge our study is the first study about the relationship between APP, PSEN1 and PSEN2 gene mutations and prognosis in our country.