Diagnosis of Alzheimer’s disease is both art and science, relying on a thorough medical history, the identification of complicating and confounding conditions, a neurological workup, as well as a number of bioassays. Still, especially at the early stages of the disease, diagnoses (especially, diagnoses that would distinguish AD from other senile dementias with different etiologies and prognoses) are less than 100% accurate.

This is particularly tragic in light of the potential for early intervention to make the greatest difference. A highly accurate, minimally invasive bioassay for early AD would be of great value to physicians treating the disease (not to mention, to their patients and their loved ones).

Progress in this direction has been reported by Maes et al., who describe a characteristic change in genome-wide mRNA levels in the peripheral blood of AD patients:

We evaluated pathomechanisms and systemic manifestations of Alzheimer disease (AD), an aging-related dementing neurodegenerative disorder, by expression profiling. Blood mononuclear cell (BMC) transcriptomes of sporadic AD subjects and aged-matched normal elderly controls (NEC) were compared using the human NIA microarray. Relative to the NEC samples, the Alzheimer BMC exhibited a significant decline in the expression of genes concerned with cytoskeletal maintenance, cellular trafficking, cellular stress response, redox homeostasis, transcription and DNA repair. We observed decreased expression of several genes which may impact amyloid-beta production and the processing of the microtubule-associated protein tau. … BMC are highly accessible and may reflect molecular events germane to the neuropathophysiology of AD.

The particular genes affected are interesting in and of themselves; I wouldn’t have necessarily predicted that amyloid ß and tau processing phenotypes would be detectable in lymphocytes. The fact that they are suggests that the molecular defects in AD are present throughout the body, but have pathological outcomes only in the brain.

From the standpoint of diagnostics, however, the nature of the specific gene expression profile is less important than the observation of a profile per se: To the extent that this is reproducible, the blood cell mRNA profile could form the basis of a microarray-based diagnostic blood test that would provide unambiguous identification of AD (vs. other senile dementias, or other conditions that can confound diagnosis).

It remains to be seen how early in the progression of the disease this expression profile emerges, or whether its magnitude tracks the severity of the disease. If it is shown to be a leading indicator of pathology, a diagnostic tool of this kind could be invaluable in the preventive care of Alzheimer’s disease.