Review and hypothesis: the genetics of alzheimer disease

Fatemeh Roshani,1 Sajjad biglari,2 Milad gholami,3 Atefeh sohan forooshan moghadam,4,* Emran esmaeilzade,5 Mohsen soosanabadi,6

1. Nourdanesh Institute of Higher Education,Meyme,Esfahan,Iran
2. Genetics department, Jiroft university of medical sciences, Jiroft,Iran
3. Genetics deartment, Shahid beheshti university of medical sciences (SBMU), Tehran, Iran
4. Nourdanesh Institute of Higher Education,Meyme,Esfahan,Iran
5. Genetics research center, University of social welfare and rehabilitation sciences (USWR), Tehran, Iran.
6. Genetics research center, University of social welfare and rehabilitation sciences (USWR), Tehran, Iran.

Abstract

Introduction

Alzheimer’s disease (ad) is the most common type of dementia in the elderly population. three genes have been identified as responsible for the rare early-onset familial form of the disease: the amyloid precursor protein (app) gene, the presenilin 1 (psen1) gene and the presenilin 2 (psen2) gene. mutations in these genes, however, account for less than 5% of the total number of ad cases. the remaining 95% of ad patients are mostly sporadic late-onset cases, with a complex aetiology due to interactions between environmental conditions and genetic features of the individual.

Methods

In this paper, we review the most important genes supposed to be involved in the pathogenesis of ad, known as susceptibility genes, in an attempt to provide a comprehensive picture of what is known about the genetic mechanisms underlying the onset and progression of ad.

Results

As a result, a large proportion of the heritability of ad continues to remain unexplained by the currently known disease genes. it seems likely that much of this “missing heritability” may be accounted for by rare sequence variants, which, owing to recent advances in high-throughput sequencing technologies, can now be assessed in unprecedented detail.

Conclusion

This review considers the three loci which have been shown to be associated with early-onset ad: amyloid precursor protein, presenilin (ps)-l and ps-2. mutations in these genes seem to be associated with overproduction of the 42-amino acid form of β-bamyloid, suggesting that this may be a central pathological process in ad. we conclude that a better understanding of the complex etiology that underlies ad may be achieved likely through a multidisciplinary approach that combines clinical and neurophysiological characterization of ad subtypes and in vivo functional brain imaging studies with molecular investigations of genetic components.

Keywords

Alzheimer’s disease (ad),genetic,gene.