Is it Possible to Prevent Early-onset Alzheimer’s Disease?

There is growing interest in amyloid beta (Aβ) lowering therapies for pre-symptomatic Alzheimer’s disease (AD). In collaboration with the Dominantly Inherited Alzheimer Network (DIAN) investigators, Bateman et al. (2012) report findings from imaging and biomarker assessments in pre-symptomatic hereditary Alzheimer’s disease (AD). These findings are important in identifying when individuals are most at risk of developing AD, as well as being critical for drug development to prevent and treat AD.

How Long Before Symptoms Appear?

By following (using imaging and body-fluid biomarkers) many families with a specific genetic variant (autosomal dominant) of Alzheimer’s disease worldwide, researchers found that age at onset rarely varies from generation to generation. Therefore, each genetic mutation carrier knows roughly how many pre-symptomatic years he or she can expect.

The DIAN study showed changes in levels of amyloid beta 42 (Aβ42) in cerebrospinal fluid (CSF). Amyloid beta 42 is a measureable biomarker that accompanies the depositing of amyloid beta plaques in the brain – a symptom of AD. This biomarker can be detected 25 years before an individual’s symptoms begin. This implies that prevention may need to begin 25 years or more before the expected onset of symptoms in those with the specific genetic mutations for autosomal dominant Alzheimer’s disease.

Until the DIAN data appeared, most AD researchers estimated that amyloid beta accumulation in the brain began 10 to 15 years before symptoms appeared.

A recent study has also suggested that lifelong reduction of amyloid beta levels by approximately 50% may be enough to prevent Alzheimer’s disease while producing no obvious negative effects.

Now it is known that, at least for specific hereditary variants (autosomal dominant) Alzheimer’s disease, the onset — or at least the initiation of the abnormal metabolism that leads to amyloid beta accumulation in the brain — is likely to be a decade earlier.

Because features of Alzheimer’s disease develop in all patients with Down’s syndrome by 45 years of age, it also suggests that clinical trials of amyloid beta-lowering therapies should begin no later than 20 years of age in those with Down’s syndrome.

Are You At Risk?

If you have AD cases among your closest blood relatives (eg parents) and you are around 40 years old, this might be a good time to seek specialist information. Some scientists are also suggesting that early concern be extended to other at-risk populations such as those with brain abnormalities/injuries, who may benefit from lifelong management of amyloid-beta metabolism.

In summary, lifelong control of amyloid beta metabolism may need to be regarded in the same way that we now think of lifelong control of cholesterol metabolism.

The lesson of the DIAN study and other studies is that reducing the risk of AD requires a long-term and possibly lifelong effort.

References and Further Reading

  • Bateman RJ, Xiong CJ, Benzinger TLS, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie XY, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC. Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease. New Engl J Med. 2012: 367: 795-804.
  • DeKosky ST, Ikonomovic MD, Gandy S. Traumatic brain injury–football, warfare, and long-term effects. The New England journal of medicine. 2010: 363: 1293-1296.
  • Gandy S. PERSPECTIVE Prevention is better than cure. Nature. 2011: 475: S15-S15.
  • Gandy S. Lifelong management of amyloid-beta metabolism to prevent Alzheimer’s disease. The New England journal of medicine. 2012: 367: 864-866.
  • Gandy S, Dekosky ST. APOE epsilon4 status and traumatic brain injury on the gridiron or the battlefield. Science translational medicine. 2012: 4: 134ed134.
  • Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, Hoyte K, Gustafson A, Liu Y, Lu Y, Bhangale T, Graham RR, Huttenlocher J, Bjornsdottir G, Andreassen OA, Jonsson EG, Palotie A, Behrens TW, Magnusson OT, Kong A, Thorsteinsdottir U, Watts RJ, Stefansson K. A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature. 2012: 488: 96-99.
  • Sperling RA, Jack CR, Aisen PS. Testing the Right Target and Right Drug at the Right Stage. Science translational medicine. 2011: 3.

Last Reviewed 14/Mar/2014

 

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Whilst wielding a couple of dumbbells in a gym class in 2003, Kate experienced an epiphany around the lack of accepted best practice guidelines when it came to staying well and avoiding disease. Kate realized that she had no chance of slowing her own aging process unless she became better educated about her options.
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