Search

Your search keyword '"Kinhult Ståhlbom, A"' showing total 3 results
Start Over Author "Kinhult Ståhlbom, A" Publisher biomed central
3 results on '"Kinhult Ståhlbom, A"'

2. The effects of different familial Alzheimer’s disease mutations on APP processing in vivo

Author

Henrik Zetterberg, Kaj Blennow, Håkan Thonberg, Maria Eriksdotter, Steinunn Thordardottir, Ove Almkvist, Anne Kinhult Ståhlbom, and Caroline Graff

Subjects
0301 basic medicine, medicine.medical_specialty, Heterozygote, Neurology, Cognitive Neuroscience, Clinical Neurology, Disease, Pathogenesis, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, Cerebrospinal fluid, Apolipoproteins E, Mutation Carrier, Alzheimer Disease, medicine, Amyloid precursor protein, PSEN1, Genetics, Presenilin-1, Humans, Family, biology, business.industry, Research, Middle Aged, Pathophysiology, 030104 developmental biology, Cross-Sectional Studies, Immunology, Mutation, biology.protein, Neurology (clinical), business, Neuroscience, Alzheimer’s disease, 030217 neurology & neurosurgery, Biomarkers
Abstract

Background Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer’s disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individuals carrying FAD mutations can give valuable insights into the earliest stages of the disease where therapeutic interventions are thought to be the most effective. Methods In the current cross-sectional study, products of APP processing (e.g., sAPPα, sAPPβ, Aβ38, Aβ40 and Aβ42) were measured in the cerebrospinal fluid (CSF) of individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), as well as in non-mutation carriers from the same families. Results We observed pathological APP processing in presymptomatic carriers of FAD mutations, with different profiles of APP and Aβ isoforms in the three mutation carrier groups, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), except for the well-established decrease in CSF Aβ42 that was found with all mutations. Conclusions These findings add to the current evidence that AD pathophysiology differs between disease-causing mutations and can be monitored in the presymptomatic disease stage by CSF analyses. This may also be important from a therapeutic standpoint, by opening a window to monitor effects of disease-modifying drugs on AD pathophysiology.

Published
2017

3. Reduced penetrance of the <italic>PSEN1</italic> H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study.

Author

Thordardottir, Steinunn, Rodriguez-Vieitez, Elena, Almkvist, Ove, Ferreira, Daniel, Saint-Aubert, Laure, Kinhult-Ståhlbom, Anne, Thonberg, Håkan, Schöll, Michael, Westman, Eric, Wall, Anders, Eriksdotter, Maria, Zetterberg, Henrik, Blennow, Kaj, Nordberg, Agneta, and Graff, Caroline

Subjects
GENETICS of Alzheimer's disease, GENETIC mutation, ALZHEIMER'S disease diagnosis, FLUORODEOXYGLUCOSE F18, POSITRON emission tomography, CLINICAL trials
Abstract

Background: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years. Methods: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017. They underwent repeated clinical evaluations, neuropsychological assessments, and cerebrospinal fluid analyses, as well as brain imaging examinations with structural magnetic resonance, [18F]fluorodeoxyglucose positron emission tomography, and [11C]Pittsburgh compound B positron emission tomography. Results: Brother A was followed between 44 and 64 years of age. Cognitive symptoms due to Alzheimer's disease set in at the age of 54. Gradual worsening of symptoms resulted in admittance to a nursing home owing to dependence on others for all activities of daily living. He showed a curvilinear decline in cognitive function on neuropsychological tests, and changes on magnetic resonance imaging, positron emission tomography, and biomarkers in the cerebrospinal fluid supported a clinical diagnosis of Alzheimer's disease. Brother A died at the age of 64 and fulfilled the criteria for definitive Alzheimer's disease according to neuropathological examination results. Brother B was followed between the ages of 43 and 65 and showed no cognitive deterioration on repeated neuropsychological test occasions. In addition, no biomarker evidence of Alzheimer's disease pathology was detected, either on imaging examinations or in cerebrospinal fluid. Conclusions: The average (SD) age of symptom onset for PSEN1 H163Y is 51 ± 7 years according to previous studies. However, we present a case of a biomarker-verified reduction in penetrance in a mutation carrier who was still symptom-free at the age of 65. This suggests that other genetic, epigenetic, and/or environmental factors modify the onset age. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results