The lifetime risk for AD in the general population is 12.1% in men and 20.3% in women by age 85. Most of the increased risk in relatives of affected individuals is not due to mendelian inheritance, this familial aggregation results from a com plex genetic contribution involving one or more incompletely penetrant genes that act independently, from multiple interacting genes, or from some combination of genetic and environmental factors.

Approximately 7% to 10% of patients, however, have a monogenic highly penetrant form of AD that is inherited in an autosomal dominant manner. In the 1990s, four genes associated with AD were identified (Table 1). Pathogenic variants in three of these genes – encoding the β-amyloid precursor protein (βAPP), presenilin 1, and presenilin 2 – lead to autosomal dominant AD. The fourth gene, APOE, encodes apolipoprotein E (apoE), the protein component of several plasma lipoproteins. Variants in APOE are not associated with monogenic AD. Rather, as we saw in Chapter 9, the ε4 allele of APOE modestly increases susceptibility to non-familial AD and influences the age at onset of at least some of the monogenic forms.

Table1. Genes and Proteins Associated With Inherited Susceptibility to Alzheimer Disease

The identification of the four genes associated with AD has provided great insight not only into the pathogenesis of monogenic AD but also, as is commonly the case in medical genetics, into the mechanisms that under lie the more common form, nonfamilial or sporadic AD. Indeed, overproduction of one proteolytic product of βAPP, called the Aβ peptide, appears to be at the center of AD pathogenesis, and the currently available experimental evidence suggests that the βAPP, presenilin 1, and presenilin 2 proteins all play a direct role in the pathogenesis of AD.

اخر الاخبار

اخبار العتبة العباسية المقدسة

دار الكفيل تنهي طباعة كتاب (لمَ لا) تمهيدًا لمناقشته في ملتقى غيث السماء القرآني الثاني

العتبة العباسية المقدسة تطلق مسابقتها الثقافية بذكرى ولادة الإمام زين العابدين (عليه السلام)

العتبة العباسية المقدسة تكرّم 1000 طالبة من المرتديات العباءة العراقية في مدارس الديوانية

العتبة العباسية المقدسة تؤكد أهمية الحجاب كجزء من منظومة الواجبات الشرعية

المزيد

الآخبار الصحية

الخبز الأسمر أم الأبيض.. أيهما أفضل لضبط سكر الدم؟

عقاقير التخسيس و"الانتحار".. الحكومة الأميركية تحسم الجدل

الهرم الغذائي الجديد.. لماذا يعد "انقلابا" في خارطة الطعام؟

لحماية ظهرك وقلبك في آن واحد.. ما وضعية النوم الصحيحة؟

المزيد

الآخبار التكنلوجية

كيف يعزز الضوء الطبيعي تفكيرك وانتباهك خلال اليوم

سابقة.. طاقم من محطة الفضاء الدولية يعود إلى الأرض مبكرا

منصات التواصل تضرّ بنفسية المراهقين… والفتيات الأكثر تأثرا

ابتكار ألماني قد يغيّر مستقبل صناعة البلاستيك

المزيد

مواضيع ذات صلة

The Genetics of mtDNA Disease

The APOE Gene Is an Alzheimer Disease Susceptibility Locus

Molecular Testing for Spinal Muscular Atrophy

Genetics of Spinal Muscular Atrophy

The Phenotypes of Spinal Muscular Atrophy

Chondrodysplasias are Caused by Mutations in Genes Encoding Type II Collagen & Fibroblast Growth Factor Receptors

The Genetics of Osteogenesis Imperfecta

Molecular Abnormalities of Collagen in Osteogenesis Imperfecta

Prenatal Diagnosis of Hereditary Genetic Diseases

Prenatal Diagnosis of Non-hereditary Genetic Diseases

Clinical Applications of Gene Testing in Muscular Dystrophy

The Genetics of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy