Aug 042011
 
alzheimer's and genetics

New guidelines have been developed for the field of Alzheimer’s disease. They were published in the June edition of Genetics in Medicine, and jointly issued by the American College of Medical Genetics and the National Society of Genetic Counselors.

The guidelines distinguish between genetic testing for dominantly inherited AD genes and that for the Alzheimer’s susceptibility gene, ApoE . The three early-onset familial AD genes — presenilin-1 (PS1), presenilin-2 (PS2) and amyloid precursor protein (APP) — confer almost 100 percent risk of developing AD, usually before the age of 60. Children of parents with the disease have a 50 percent chance of inheriting the gene, and may request pre-symptomatic testing. The guidelines lay out several strong recommendations for this type of predictive testing.

In contrast to dominantly inherited genes, testing for the AD susceptibility gene ApoE is a completely different case. The fourth gene, APOE-e4 on chromosome 19, is linked to a greater risk of susceptibility for developing late-onset Alzheimer’s. Late-onset AD is the more common form of the disease manifested after the age of 55 and generally associated with old age. APOE-e4 is a variant form of a gene that encodes the production of a protein called apolipoprotein E, which may play a role in repairing connections between brain cells. People with one copy of APOE-e4 have a greater risk of getting Alzheimer’s than people with other forms of the gene, and people with two copies of APOE-e4 have an even greater risk. Although carrying a copy of the ApoE4 risk allele increases the odds of getting AD by several fold, many people with the risk allele do not get the disease, while others without the allele do develop AD. The guidelines do not advocate for such testing.

The authors hope the guidelines will help to ensure that genetic testing for AD is performed in situations where it will provide useful information, and that patients and family remembers receive accurate information on the meaning of the results.

Goldman JS, Hahn SE, Catania JW, Larusse-Eckert S, Butson MB, Rumbaugh M, Strecker MN, Roberts JS, Burke W, Mayeux R, Bird T. Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011 Jun;13(6):597-605.

Michael S. Rafii, M.D., Ph.D.

Director, Memory Disorders Clinic
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
University of California San Diego

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

Learn More

Apr 212011
 

Dear Readers,

In a recent post this month, I focused on a study from Korea that examined whether the cardiovascular risk factors had similar effects on dementia risk in the Korean population as compared to Western populations. In this blog post, I discuss the latest data from Korea that examines the association of APOE e4 and depression to incident (development of ) dementia in elderly Koreans.

This study used data from the 10/66 International Dementia Research Program in Developing Countries. All persons aged 65 or older from two geographic areas in Gwangiu, South Korea, were asked to participate in this study with follow-up examinations occurring two years later.

Participants completed a variety of questionnaires that included: (1) 30 questions from Korean Geriatric Depression scale ( including supplemental items from the Geriatric Depression Scale, Beck Depression Inventory, and the Center for Epidemiologic Studies Depression Scale; (2) a review of alcohol history, physical activity, disability, vascular risk factors and measured obesity (BMI>25 kg/m2); (3) cognitive assessment testing (Mini-mental state examination, the Clinical dementia rating (CDR) scale, Instrument Activities of Daily living scale); and (4) APOE e4 genotyping.

A diagnosis of dementia was determined using standard criteria for dementia, Alzheimer’s Disease (AD) and vascular dementia (VaD) by committee. The diagnosis of clinical depression was determined by utilizing validated cutoff scores (against psychiatric diagnoses specific for the Korean population).

Of the initial 732 participants, 518 (83 percent) completed all evaluations at follow-up with 45 participants developing dementia (34 with AD, seven with VaD and four with “other dementia”) over a two-year period. APOE e4 and baseline depression were significantly associated with the incident dementia. When other factors were added to the models, the association between APOE 4 and dementia were unchanged, whereas the association of depression and dementia was no longer significant. Persons with a +APOE e4 genotype / + depression had a nine- fold increased risk of developing dementia compared to those with -APOE e4 genotype/- depression. When other factors were added to this model, the associations were weakened but still remained significant. Gender differences were noted, in that, men had approximately a four times higher risk of developing dementia if they were classified as +APOE e4 /+depression compared to + APOE e4/+ depression women.

This study adds to the few population based studies from Asia that have examined the association of depression and APOE e4 to the development of dementia. The gender differences noted for risk of dementia are interesting, yet it is unclear as to the possible biological mechanisms underlying these findings. Nevertheless, this study supports findings from Western studies regarding the role of depression and APOEe4 to increased risk of dementia, and suggests that perhaps treating a potentially modifiable risk factor such as depression could modify this relationship and delay the development of dementia.

Here are three articles you can refer to, if you wish to learn about this particular study or the latest research on APOE4, depression and dementia in the Korean population:

Thanks for reading.

Neelum T. Aggarwal, M.D.
Steering Committee Member, ADCS
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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