アルツハイマー病のスクリーニングバイオマーカー

抄録

In the usual sense, the disease biomarker may imply a diagnostic one. Previously, such a diagnostic biomarker of Alzheimer's disease (AD) was highly desired because the diagnosis of AD was exclusion one. Once dementia was diagnosed, a great number of diseases causing dementia were excluded and finally the diagnosis of AD was made. In these 20 years, the biology of AD has been greatly advanced. The earliest symptom is loss of episodic memory, which is followed within several years by impairment of other cognitive domains. CSF from AD patients contains high levels of phosphorylated and total tau, and low levels of Abeta42. This is the case even in the period of mild cognitive impairment (MCI). Furthermore, refined imaging techniques, especially MRI has made it possible to prevent us from misdiagnosing other diseases as AD. Thus, at well-equipped medical centers, the diagnostic accuracy may have already reached more than 90%. In view of the temporal profile of AD, Abeta accumulation would precede neurofibrillary tangle formation that is associated with cognitive symptoms by more than a decade. As this period accompanies none of the cognitive symptoms, we should develop the method of screening cerebral Abeta accumulation by means of blood test. According to the data based on transgenic mice (Tg2576), plasma (and CSF) Abeta42 levels decrease when Abeta42 starts to accumulate in the brain. If it is true with humans, long-term follow-ups of plasma Abeta42 levels may warn potential Abeta deposition, and such blood-test-positive people should subsequently have sophisticated examinations including MRI or amyloid imaging. These at-risk people could be advised for the appropriate life style, especially foods and exercise, and if needed, may be given gamma modifier. This strategy should at least postpone the development of AD in an individual several years, and in this way, we should make every attempt to decrease the number of AD patients.