Journal
ALZHEIMERS RESEARCH & THERAPY
Volume 9, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13195-017-0234-1
Keywords
Alzheimer's disease; Amyloid precursor protein; Biomarkers; Cerebrospinal fluid; Genetics
Categories
Funding
- Swedish Brain Power
- Swedish Alzheimer Foundation
- Torsten Soderberg foundation
- Swedish Dementia Association
- Gun and Bertil Stohne's Foundation
- Gamla Tjanarinnors Foundation
- Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet
- Swedish Research Council
- Karolinska Institutet PhD-student funding
- Swedish Brain Foundation
- King Gustaf V and Queen Victoria's Free Mason Foundation
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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., sAPP alpha, sAPP beta, A beta(38), A beta(40) and A beta(42)) 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 A beta 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 A beta(42) 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.
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