Since the PSEN1 E280A anomaly is autosomal dominant, only one copy of the gene is required to cause disease.
This woman did not start showing signs of Alzheimers till she remained in her early 70s when carriers of the anomaly usually show signs of the disease in their 40s or 50s and pass away from it shortly after. She died at the age of 77 in 2020 from metastatic melanoma.
” This is a ground-breaking case for Alzheimers illness and has actually currently opened new paths for treatment and avoidance, which were presently pursuing with some collaborators. This work is now bringing light into a few of the mechanisms of resistance to Alzheimers disease” says investigator Yakeel T. Quiroz, Ph.D
. Quiroz is director of the Multicultural Alzheimer Prevention Program (MAPP) at Mass General, an Associate Professor of Psychology in the Department of Psychiatry at Harvard Medical School, and Paul B. and Sandra M. Edgerley MGH Research Scholar 2020-2025.
The essential difference in the Colombian females ability to fend off the illness for three years appeared to be that in addition to having the PSEN1 E280A mutation, she was likewise a carrier of both copies of a mutation referred to as APOE3 Christchurch.
The APOE family of genes controls the production of apolipoproteins, which transport lipids (fats) in blood and other bodily fluids.
The APOE2 version is understood to be protective against Alzheimers dementia, while the APOE4 version is linked to an increased danger for the illness.
APOE3, the most typical version, is not generally associated with either minimized or increased threat for Alzheimers.
As Quiroz and colleagues now report in the neuropathology journal Acta Neuropathologica, the lady did, in truth, have pathologic functions of Alzheimers illness in her brain, but not in areas of the brain where the hallmarks of Alzheimers are normally found.
” This patient gave us a window into numerous completing forces– irregular protein accumulation, inflammation, lipid metabolic process, homeostatic mechanisms– that either protect or promote versus illness development, and start to explain why some brain regions were spared while others were not,” states Justin Sanchez, AB, co-first author, and an investigator at MGH Neurology.
Researchers determined in Alirias brain a distinct pattern of unusual aggregation or “clumping” of tau, a protein understood to be modified in Alzheimers disease and other neurologic disorders.
In this case, the tau pathology mainly spared the frontal cortex, which is very important for judgment and other “executive” functions, and the hippocampus, which is essential for memory and learning.
Instead, the tau pathology involved the occipital cortex, the area of the brain at the back of the head that controls visual perception.
The occipital cortex was the only major brain region to display typical Alzheimers features, such as persistent swelling of protective brain cells called microglia, and reduced levels of APOE expression.
” Thus, the Christchurch version might affect the distribution of tau pathology, regulates age at beginning, intensity, progression, and medical presentation of [autosomal dominant Alzheimers illness], recommending possible therapeutic strategies,” the researchers compose.
” It is seldom that we have good surprises while studying familial Alzheimers illness brains.- says co-first author, Diego Sepulveda-Falla, MD, Research Lead at University Medical Center Hamburg-Eppendorf in Hamburg, Germany.
” This exceptional case is an experiment developed by nature that teaches us a method to prevent Alzheimers: lets observe, learn and imitate nature,” concludes Francisco Lopera, MD, director of the Neuroscience Group of Antioquia in Medellín, Colombia. Lopera is a co-senior author and the neurologist who discovered this household and has been following them for the last 30 years.
Reference: “Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote secured against autosomal dominant Alzheimers dementia” by Diego Sepulveda-Falla, Justin S. Sanchez, Maria Camila Almeida, Daniela Boassa, Juliana Acosta-Uribe, Clara Vila-Castelar, Liliana Ramirez-Gomez, Ana Baena, David Aguillon, Nelson David Villalba-Moreno, Jessica Lisa Littau, Andres Villegas, Thomas G. Beach, Charles L. White III, Mark Ellisman, Susanne Krasemann, Markus Glatzel, Keith A. Johnson, Reisa A. Sperling, Eric M. Reiman, Joseph F. Arboleda-Velasquez, Kenneth S. Kosik, Francisco Lopera and Yakeel T. Quiroz, 15 July 2022, Acta Neuropathologica.DOI: 10.1007/ s00401-022-02467-8.
The study was moneyed by the National Institutes of Health, MGH Executive Committee on Research (MGH Research Scholar Award), Alzheimers Association, the Deutsche Forschungsgemeinschaft, Universidad de Antioquia, the Werner Otto Stiftung, and the German Federal Ministry of Education and Research.
” This is a ground-breaking case for Alzheimers illness and has actually currently opened brand-new courses for treatment and prevention, which were currently pursuing with some partners. This work is now bringing light into some of the mechanisms of resistance to Alzheimers illness” says detective Yakeel T. Quiroz, Ph.D
. Quiroz is director of the Multicultural Alzheimer Prevention Program (MAPP) at Mass General, an Associate Professor of Psychology in the Department of Psychiatry at Harvard Medical School, and Paul B. and Sandra M. Edgerley MGH Research Scholar 2020-2025.
” It is hardly ever that we have nice surprises while studying familial Alzheimers disease brains.- states co-first author, Diego Sepulveda-Falla, MD, Research Lead at University Medical Center Hamburg-Eppendorf in Hamburg, Germany.
The scientists believe that the females brain could provide important info about treating dementia.
A mutation referred to as APOE3 Christchurch appears to have actually protected the lady.
Due to a rare genetic anomaly, Aliria Rosa Piedrahita de Villegas must have had Alzheimers disease in her 40s and passed away from it in her 60s.
Her brain is now supplying crucial info on the pathology of dementia and potential treatments for Alzheimers illness given that she lived dementia-free into her 70s.
The woman, from Medellin, Colombia, was a member of an extended family with a mutation in the PSEN1 gene, as scientists at Massachusetts General Hospital (MGH) and other institutions initially reported in 2019.