Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ Key Points ++ Disease summary: Alzheimer disease (AD) is the most common form of dementia. It is characterized by debilitating and progressive episodic memory loss, difficulty with language and decision making, and (in advanced stages) loss of motor control, incontinence, and mutism. The neuropathologic hallmarks of the AD brain include an abundance of senile plaques largely composed of beta-amyloid (Aβ) deposits and neurofibrillary tangles made up of tau protein. While these features are consistently observed in autopsies of AD patients, the exact role that these proteins play in AD pathogenesis is still unclear. Most patients with AD begin developing symptoms after 60 years of age, although in the rare cases of autosomal dominantly inherited AD symptoms typically manifest at an earlier age. Although risk for AD increases with age, AD is not a symptom of normal aging. Differential diagnosis: Treatable diagnoses: depression, chronic drug intoxication, chronic central nervous system (CNS) infection, thyroid disease, vitamin deficiencies (particularly B12 and thiamine), CNS angiitis, and normal-pressure hydrocephalus (NPH) Other neurodegenerative disorders: vascular dementia, diffuse Lewy body syndrome, Parkinson disease, Pick disease, Creutzfeldt-Jakob disease, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Monogenic forms: Rare cases of very early-onset familial AD (FAD) follow a Mendelian autosomal dominant inheritance pattern. Approximately 70% of FAD cases can be explained by mutations in one of three genes: PSEN1, PSEN2, and APP. Family history: The average person has a 10% to 12% chance of developing AD in his or her lifetime. First-degree relatives of patients with AD have a 20% to 44% lifetime risk for the disease. Twin studies: Monozygotic twins show a 60% concordance rate for AD. Environmental factors: Risk factors include female gender, lower level of education, and history of head trauma. Genome-wide Associations: Recent large-scale genome-wide association studies (GWASs) have identified multiple genetic loci associated with AD risk (Table 124-1). Of these results however, even the most robust marker for AD susceptibility, the ε4 allele of APOE, is neither necessary nor sufficient for AD diagnosis. Pharmacogenomics: While several studies have begun stratifying AD patients based on genetic markers to test for differential response to treatment, at present no consistently replicated pharmacogenomic associations have been observed for AD therapies. ++Table Graphic Jump LocationTable 124-1Molecular Genetic Testing For Alzheimer DiseaseView Table||Download (.pdf) Table 124-1 Molecular Genetic Testing For Alzheimer Disease Gene (Location) Name Form of AD Inheritance Pattern Penetrance Available Testing APPa(21q21.3) Amyloid precursor protein FAD Autosomal dominant 100% Clinically available for adults but rare PSEN1(14q24.2) Presenilin 1 FAD Autosomal dominant 100% Clinically available for adults and prenatal testing PSEN2(1q42.13) Presenilin 2 FAD Autosomal dominant 95% Clinically available for adults but rare APOE(19q13.32) Apolipoprotein E Sporadic AD Complex N/A Clinically available for adults through direct-to-consumer testing aAt least one variant within the APP gene has been demonstrated to be protective for AD. However, to date clinical genetic ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Download the Access App: iOS | Android Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.