We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Exploring the Etiology of Alzheimer Disease Using Molecular Genetics

Corinne L. Lendon, PhD; Frank Ashall, DPhil; Alison M. Goate, DPhil
JAMA. 1997;277(10):825-831. doi:10.1001/jama.1997.03540340059034.
Text Size: A A A
Published online


Alzheimer disease (AD), the most common cause of dementia in the elderly, exists in both familial and sporadic forms. Genetic studies have led to the identification of 3 genes, β-amyloid precursor protein (APP), presenilin-1 (PS1), and presenilin-2 (PS2), which, when mutated, can cause familial forms of AD. Mutations in each of these genes result in elevated levels of Aβ42/43, a proteolytic processing fragment of APP that is deposited in brains of AD patients. Transgenic mice carrying AD-causing mutations in APP develop spontaneous agerelated β-amyloid (Aβ) deposition and memory impairment. Genetic linkage and association studies have also shown that the ϵ4 allele of the apolipoprotein E (APOE) gene increases risk for AD in a dose-dependent manner in both familial and sporadic forms of AD and may account for as much as 50% of the attributable risk. APOE genotyping may be useful both as an adjunct to diagnosis and in identifying patient groups for therapeutic intervention. While the biological basis for the association of APOEϵ4 with AD is not known, age of onset and Aβ deposition are positively correlated with ϵ4 allele dosage in some cases, suggesting that this risk may also be mediated directly or indirectly through Aβ. Because 50% of AD cases have no APOE ϵ4 alleles and families showing mendelian inheritance of AD exist in whom there are no mutations in any of the APP, PS1, or PS2genes, it is likely that there are additional AD risk factors, both genetic and environmental, still to be identified.


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.