Panel Releases First Guidelines for Assessing Early Diagnostic for Alzheimer's Disease

Alzheimer's Association
Thursday, 9 April 1998

There is growing evidence that the destructive forces that kill brain cells in Alzheimer's disease start many years before we can detect the presence of this silent killer with current methods of clinical evaluation. Early and accurate diagnosis of Alzheimer's is a critical first step in the effort to delay the onset of disabling symptoms and the eventual prevention of the disease, according to the Alzheimer's Association.

To accelerate the development of the technologies needed for early diagnosis and stimulate further research, an international group of scientists convened by the Alzheimer's Association has proposed the first set of criteria for assessing all proposed molecular and biochemical markers for Alzheimer's disease.

"We've heard many claims about possible indicators for Alzheimer's disease, such as an eye drop test, a skin test and several possible genetic links," said Zaven Khachaturian, Ph.D., director of the Alzheimer's Association Ronald & Nancy Reagan Research Institute. "Each time there is an announcement, the Association and its local chapters, doctors and other healthcare professionals get bombarded with questions. This paper proposes the first standard against which these claims can be assessed," Khachaturian said.

The new criteria are contained in "Consensus Report of the Working Group on: 'Molecular and Biochemical Markers of Alzheimer's Disease,'" which appears in the April 1998 issue of the journal Neurobiology of Aging. The recommendations were developed through a consensus process begun in September 1997 by a working group sponsored by the Reagan Institute and the National Institute on Aging (NIA). The work was underwritten in part by an unrestricted grant to the Alzheimer's Association from Athena Neurosciences, Inc.

According to John Growdon, M.D., director of the Alzheimer's Disease Center at Massachusetts General Hospital and chair of the working group's advisory committee, a marker for Alzheimer's disease should be reliable, precise, reproducible, non-invasive, simple to perform, inexpensive and not threatening to the patient. "This is a significant step toward our larger goal of improving the overall diagnostic process, and more particularly, improving early detection of Alzheimer's disease," Growdon said.

Early detection is critical for several reasons, according to the Association. First, it enables scientists to track the course of the disease, and test the effectiveness of potential treatments to slow its progression. Second, as more treatments become available in coming months and years, it will permit physicians to prescribe drugs earlier in the disease process, when they can be most beneficial. Finally, early diagnosis enables those with the disease to participate in planning their future, including legal, financial and care options.

Review of Current Proposed Markers

The working group reviewed published material on all recently proposed markers for Alzheimer's disease, and made the following recommendations:

For early onset familial Alzheimer's disease, it is appropriate to test for mutations in the presenilin 1, presenilin 2 and amyloid precursor protein genes.

These mutations are relatively rare. Only 120 families worldwide are currently known to carry these mutations. Testing should be limited to those with a family history of early onset Alzheimer's.

In late onset and sporadic Alzheimer's disease, detecting an e4 allele of the APOE gene can add confidence to the clinical diagnosis.

APOE testing is only appropriate after clinical evaluation yields a likely diagnosis of Alzheimer's. APOE testing cannot be used as a sole diagnostic test, and is not appropriate for asymptomatic individuals.

Among the other proposed molecular and biochemical markers for Alzheimer's disease, none has yet achieved universal acceptance nor fully met the proposed criteria for an ideal biomarker, and thus cannot be accepted for widespread use at present.

These include amyloid deposits in skin (skin test), pupil dilation in response to dilute solution of tropicamide (eye drop test), neuronal thread proteins in cerebrospinal fluid (AD7C), and serum levels of iron binding protein p97. Tests of cerebrospinal fluid for abnormal levels of indicator proteins, known as Ab 42 and tau, come closest to fulfilling the criteria for a useful biomarker.

Reagan Institute Working Groups

The Association's Reagan Institute has convened a series of working groups focused on important topics in research into Alzheimer's disease and related disorders. The mission of each working group is to develop a position paper, and, if possible, a consensus statement to help:

- Identify scientific opportunities or new research directions

- Determine the need for additional research resources

- Evaluate barriers that impede the progress of research

- Guide public policy on research

The Association plans to collaborate with the NIA on a number of these working groups. The first working group, with the NIA, published a consensus paper in September 1997 that established new guidelines for the post-mortem diagnosis of Alzheimer's.

Additional members of the advisory committee to the Working Group on Molecular and Biochemical Markers of Alzheimer's Disease are: Peter Davies, Ph.D., Albert Einstein School of Medicine, Bronx; Sid Gilman, M.D., University of Michigan, Ann Arbor; Ann Saunders, Ph.D., Duke University, Durham, NC; Dennis Selkoe, M.D., Brigham and Women's Hospital, Boston; Allen Roses, M.D., Glaxo Wellcome, Durham, NC; and John Trojanowski, M.D., Ph.D., University of Pennsylvania, Philadelphia.

For more information, or to contact Alzheimer's Association, see their website at: www.alz.org