Blood-borne Amyloid-beta Dimer Correlates with Clinical Markers of Alzheimer's Disease

As readers know, a diagnosis of Alzheimer’s disease is made based on a clinician’s judgment and observations following a variety of neuropsychological tests, lab work to rule out other causes of symptoms, and other assessments. A definitive diagnosis must wait until a post-mortem exam of the patient’s brain tissue that reveals the presence of amyloid plaques and neurofibrillary (tau) tangles. Studies have shown these plaques (especially amyloid-beta) are associated with AD and progression of the disease. Kevin J. Barnham, of the University of Melbourne, and colleagues noted that studies attempting to target amyloid-beta processing have been thwarted by the lack of validated biomarkers. However, several studies have pointed to oligomeric forms of amyloid-beta as “the toxic species that induce the neuronal dysfunction associated with AD.” These forms also include “synaptotoxic amyloid-beta dimers” that have been found post-mortem in AD brain tissue. Because there is currently no means of monitoring this promising target in live patients, Barnham and colleagues analyzed blood samples from a cohort of patients (43 with AD, 23 with mild cognitive impairment, and 52 healthy controls) using a form of mass spectroscopy to see if they could identify oligomeric forms of amyloid-beta and to see if there were differences in the level of those oligomers in healthy subjects vs. patients with AD and/or MCI. They found differences in the blood profiles between healthy patients and patients with AD and/or MCI that were consistent with the presence of two “distinct processing pathways” for amyloid precursor protein (APP) with “an amyloidogenic pathway favored in AD.” This has potential diagnostic and therapeutic implications because this finding indicated “significantly higher levels of amyloid-beta monomer and amyloid-beta dimer in the blood of AD subjects” (an increase of 16% and 35%, respectively, compared with controls). The researchers also reported that their findings correlated with other clinical markers of AD, including MMSE scores. These results indicate that “fundamental biochemical events relevant to AD” can be monitored through routine blood analysis and may be useful clinical biomarkers for AD.