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Abstract Alzheimer’s disease is the most common form of dementia, characterized by slow, progressive memory loss. As the disease progress other symptoms such as visuospatial disorientation, language impairment, executive dysfunction or frontal lobe signs develop. Also, there is significant impairment of ADL and IADL of these patients. Approximately 5% of people 65 years or older are at risk for developing Alzheimer’s dementia. The number of Americans with Alzheimer’s disease is expected to increase to 14 million by 2050, unless a cure or preventive measures can be found. This thesis aimed to study the role of TNF α 308 G/A polymorphism in the development of late onset Alzheimer’s disease (LOAD) in Egyptians. Our hypothesis was that, the presence of TNF α 308 A allele itself does not necessarily lead to development of AD, however; it leads to increased susceptibility to develop Alzheimer’s disease as it is associated with increased transcriptional activity & elevated levels of TNF. Sixty two elderly subjects aged ≥65 years participated in this study. The subjects were divided in two groups matched for age and gender. (A) Patients group: 31 elderly patients (mean age was about 75 years) diagnosed as probable Alzheimer’s disease according to The DSM-IV-TR and the NINCDS-ADRDA. The severity of dementia was staged according to Clinical Dementia Rating scale (CDRS), Activities of Daily Living (ADL) & Instrumental Activities of Daily Living (IADL). (B) Control group: 31 cognitively normal elderly subjects (mean age was about 74 years) with no evidence of any neurological or psychiatric diseases, or any medical illness that could affect cognition. After taking consent, and doing complete medical & neurological examination, neuropsychological assessment using Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Clinical Dementia Rating Scale (CDRS), Activities of Daily Living (ADL) & Instrumental Activities of Daily living (IADL) was done for all subjects. Both cases & control groups had underwent assays for detecting TNF α 308 G/A genotyping by PCR – RFLP method. The current study revealed that TNF 308 ”A” allele was associated with increased susceptibility of developing , early age of onset and more severe form of LOAD in Egyptians as we found that:- 1- The ”A” allele was significantly more prevalent in patients than controls & the ”G” allele was significantly more prevalent in controls than patients (p < 0.001). 2- The ”A” allele was significantly associated with younger age of onset of AD than the ”G” allele (p < 0.001). 3- The ”A” allele was significantly associated with longer illness duration of AD than the ”G” allele (p < 0.001). 4- The ”A” allele was significantly associated with higher CDRS score than the ”G” allele denoting more severe form of AD (p < 0.001). 5- The ”A” allele was significantly associated with lower IADL score than the ”G” allele meaning that the ”A” allele is significantly associated with more functional deterioration among patients denoting more severe form of AD (p 0.001) |