Anyone who’s worried about Alzheimer’s disease should know about Doug Whitney. Doug is what researchers have coined an “escapee” of familial Alzheimer’s disease (FAD), the rare hereditary form of Alzheimer’s caused by inheriting mutations in one of three genes (APP, PSEN1, and PSEN2). But to many in the disease community Doug represents hope, hope brought through research participation.
FAD mutations lead to an aggressive buildup of amyloid plaques in the brain. People with these mutations typically develop Alzheimer’s disease between the age of 30-50. People with FAD also have a 50% chance of passing the disease on to each of their children. To learn more visit: Youngtimers.
Looking at Doug Whitney’s family tree, one can see the devastating impact this disease has had for generations. Doug’s mother and 9 of her 13 siblings developed FAD around the age of 50, due to the inheritance of a mutation in PSEN2.
A recent New York Times article described Doug and his incredible story of “escaping” Alzheimer’s disease. Because his mother had the disease, Doug was at a 50% risk of inheriting that same PSEN2 mutation and disease. When Doug turned 50, his wife and children began watching for signs of the disease. However, as the years went by the disease never came. Twelve years later, he is still living without symptoms of FAD, well beyond what researchers call his “estimated age of onset.” Doug thought that he had been lucky and had not inherited the mutation. However, genetic testing later revealed the unimaginable: he carried the PSEN2 mutation.
How could this be possible? Researchers believe that Doug may have some genetic or environmental factors that have protected him against memory loss. Meaning understanding more about Doug could offer key insight into developing therapies that resist or prevent Alzheimer’s disease. Doug has undergone several assessments over the years, including skin biopsies, bloodwork, lumbar punctures, PET scans, MRI scans, to help researchers and the field uncover his hidden superpower (resilience to Alzheimer’s disease). The investigation into these genetic and environmental factors was recently published in a scientific article.
While researchers still do not know what has prevented Alzheimer’s disease memory loss in Doug, they believe a key finding is that while he has lots of amyloid in his brain, there is very little tau pathology (the second main disease hallmark in Alzheimer’s disease). Like Doug, the discovery of two other “escapees”, who were carriers of another FAD mutation, also showed lots of amyloid plaques in their brain, but minimal tau accumulation (Resistance to autosomal dominant Alzheimer’s in an APOE3-Christchurch homozygote: a case report – PMC, Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man). Clues are beginning to emerge that if we can stop tau from forming, we may be able to prevent the symptoms of Alzheimer’s disease.
During typical Alzheimer’s disease progression, Abeta proteins increase and aggregate into amyloid plaques and are followed by increases in abnormal tau and the formation of neurofibrillary tangles. In escapees, amyloid plaques are forming, but tau is not changing. Researchers continue their efforts to uncover what could explain this uncoupling of amyloid and tau. This includes work at UCI, where researchers introduced a potential protective variant against FAD into a mouse model of Alzheimer’s disease: APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology. This work along with the work of several other laboratories indicates neuroinflammation, such as microglia, may play a strong role in disease progression.
Doug’s story represents the importance of the relationships and partnerships between researchers, clinicians, patients and their families. Because of Doug’s dedication to be involved in research and the passion of researchers to uncover these clues, we are at the forefront of finding meaningful treatments for Alzheimer’s disease. Doug’s story sheds light on what can happen when we come together.
