Medical Research Journals

26 Aug Many Patients with Clinical Alzheimer’s Do Not Have Significant Amyloid Pathology

MedicalResearch.com Interview with: Dr. Eric Reiman MD Executive Director, Banner Alzheimer’s Institute (BAI) Chief Executive Officer, Banner Research Clinical Director of the Neurogenomics Division at the Translational Genomics Research Institute (TGen) Professor of Psychiatry, University of Arizona Director, Arizona Alzheimer’s Consortium Phoenix Arizona   Medical Research: What is the background for this study? What are the main findings? Dr. Reiman: Beta-amyloid plaque deposition is a cardinal feature of Alzheimer’s disease. Recent positron emission tomography (PET) have suggested that about one-fourth of patients with the clinical diagnosis of mild-to-moderate Alzheimer’s dementia—and more than a third of those who had no copies of the APOE4 gene, the major genetic risk factor for Alzheimer’s—do not have appreciable amyloid plaque deposition. We wondered whether this finding reflected an absence of appreciable brain amyloid, particularly in APOE4 non-carriers, or instead an underestimation of amyloid plaques using PET. In those patients with minimal plaque deposition, we also wondered what percentages had neuropathological evidence of another dementia-causing disease, neurofibrillary tangle pathology (the other cardinal feature of Alzheimer’s, or no known pathological contribution. We surveyed data from the 100 APOE4 non-carriers and 100 APOE4 carriers who had the clinical diagnosis of mild-to-moderate Alzheimer’s dementia during their last visit at any of the nation’s Alzheimer’s Disease Centers and had an autopsy performed within the next 2 years. As we reported in JAMA Neurology, 37 percent of APOE4 non-carriers and 13 percent of APOE4 carriers with a clinical diagnosis of mild-to-moderate Alzheimer’s had minimal evidence of neuritic or diffuse amyloid plaques—and those for whom we had brain samples had no evidence of increased soluble amyloid. A proportion of individuals had a different neuropathological diagnosis. While nearly half of those patients with minimal amyloid or any other pathology had extensive tangle formation, a similar percentage was found in cognitively unimpaired persons in the same age range. Our findings suggest the PET findings are correct – that a quarter of all patients (and more than a third of APOE4 non-carriers) with the clinical diagnosis of Alzheimer’s dementia do not have appreciable amyloid pathology, and that about 10 to 15 percent of patients do not have a clear explanation for their dementia.