We’ve Come This Far… New Biomarker Doors are Opening for Alzheimer’s Disease!
Some researchers suggest it is not possible to validate disease-modifying agents or drugs that can be successful in preventing or treating Alzheimer’s disease (AD) without relying on biomarkers. A biomarker is a biological characteristic that can be measured or evaluated, and an example of successful biomarkers is in coronary artery disease, where blood lipid profiling led to regulatory approval of the first statin years before it was fully proven to prevent heart attacks.
Research into Alzheimer’s disease is now moving in the same direction. Numerous CSF (cerebrospinal fluid) and neuroimaging studies are consistently validating biomarkers that indicate a high risk of developing AD. These include early changes in molecular levels of Aβ42 (amyloid beta 42) and tau, as well as the identification of amyloid deposition – specific tissue changes in the brain that lead to the characteristic formation of plaques and tangles.
CSF samples by lumbar puncture are the ideal way to obtain information about the biochemistry of the AD disease processes. Because multiple lengths of amyloid-beta peptide molecules and tau proteins (which are involved in AD) can be measured in small samples of CSF, it means that researchers can acquire information about how the brain and nervous system is responding to Alzheimer’s disease progression.
The fears of many that lumbar punctures are uncomfortable and generally unacceptable to patients are now out of date. The Alzheimer Disease Neuroimaging Initiative and AD research centers have documented how feasible and informative routine CSF analysis by lumbar puncture can be.
Although the advent of PET amyloid imaging (brain imaging) is very helpful for pre-symptomatic diagnosis of Alzheimer’s, the low level of amyloid beta 42 in cerebrospinal fluid is an equally, if not more sensitive, biomarker, indicating that cerebral amyloid beta deposition, and therefore AD development, is under way.
References and Further Reading
- Fagan AM, Head D, Shah AR, Marcus D, Mintun M, Morris JC, Holtzman DM. Decreased cerebrospinal fluid Aβ42 correlates with brain atrophy in cognitively normal elderly. Annals of Neurology. 2009: 65: 176-183.
- Morris JC, Selkoe DJ. Recommendations for the incorporation of biomarkers into Alzheimer clinical trials: an overview. Neurobiology of aging. 2011: 32: S1-S3.
- Pankevich D, Wizemann T, Altevogt B. Alzheimer’s Diagnostic Guideline Validation: Exploration of Next Steps: Workshop Summary. Washington (DC), 2012.
- Selkoe DJ. Preventing Alzheimer’s disease. Science. 2012: 337: 1488-1492.
- Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VMY, Trojanowski JQ. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Annals of Neurology. 2009: 65: 403-413.
Last Reviewed 14/Mar/2014
