Henne Holstege (Netherlands)
Amsterdam UMC
Human Genetics
Henne Holstege works at the Department of Human Genetics of the Amsterdam University Medical Center, where she heads the section of Genomics of Neurodegenerative Diseases and Aging. Holstege majored in biochemistry at Leiden University, after which she moved to Harvard Medical School to study the neurochemistry associated with satiety. She did her PhD at the Netherlands Cancer Institute, studying the genetic aberrations associated with the development of breast cancer. Meanwhile she was intrigued by the finding that reaching extreme ages often occurs within families, suggesting a genetic contribution to escaping disease. In 2010, Holstege moved to the Amsterdam UMC where in 2013, she set up the 100-plus Study cohort of cognitively healthy centenarians. With this study she aims to identify protective genetic factors, and downstream molecular factors that contribute to the prolonged maintenance of brain health. Holstege compares the centenarians with individuals who represent the other extreme of the cognitive spectrum, Alzheimer Disease patients. For this, Holstege ’s lab is involved in large international collaborative efforts to sequence thousands of Alzheimer Disease cases and cognitively healthy controls. Holstege won the Alzheimer Research Prize 2020 from the Hans und Ilse Breuer Foundation. For more information see: www.holstegelab.eu; 100plus.nl; www.alzheimergenetics.org

Moderator of 1 Session

 Conference Calendar

SORL1

Session Time
11:10 - 13:10
Session Type
SYMPOSIUM
Date
Sat, 09.03.2024
Room
Auditorium III + IV
Chair(s)

Presenter of 1 Presentation

 Conference Calendar

ESCAPING DEMENTIA UNTIL EXTREME AGES: WHAT CAN COGNITIVELY HEALTHY CENTENARIANS TEACH US?

Session Name
2220 - PLENARY LECTURE 01, 02 AND 03 (ID 7)
Session Type
PLENARY LECTURE
Date
Tue, 05.03.2024
Session Time
16:35 - 18:05
Room
Auditorium I
Presenter
Lecture Time
17:05 - 17:35

Abstract

Abstract Body

A Dutch woman who died at age 115 without any symptoms of cognitive decline proved that cognitive decline is not inevitable. This leads to the question: how can cognitive health be maintained during human aging? To learn about the molecular mechanisms underlying this extraordinary phenomenon, we set up the 100-plus Study, a longitudinal cohort study of cognitively healthy centenarians with the primary aim to identify protective genetic and biomolecular factors that associate with the escape of cognitive decline.

Currently the cohort includes more than 450 healthy centenarians whom we subject annually to an extensive neuropsychological testing battery. We collect medical, family and life history, and various biomaterials including blood samples, faeces samples, and ~30% of the centenarians agrees to post-mortem brain donation.

Compared to individuals born in the same birth-year, centenarians are mostly from the higher social economic classes, have a relatively high education, and slightly more children, and they are mostly optimistic individuals. After reaching 100 years in cognitive health, many centenarians remain cognitively healthy until death. Centenarians are depleted with genetic elements associated with increased risk of Alzheimer's Disease, while they are enriched with protective genetic elements. This genetic protection is especially focused on maintaining a functional immune- and endolysosomal system. Amyloid-beta is widely spread in centenarian-brains, while loads stay low. Some centenarians are resistant, while others are resilient to tau and/or other neuropathological hallmarks of neurodegenerative disease. Based on specific aspects of their brain proteome, centenarian-brains are up to decades younger than expected according to their age, which pinpoints important proteomic determinants of maintaining brain health.

In my presentation, I will cover the latest results of the 100-plus Study, covering neuropsychological, genetic, neuropathological, brain proteomic, and immunological findings.

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