Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The relevance of cerebrospinal fluid -synuclein levels to sporadic and familial Alzheimer's disease
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Show others and affiliations
Number of Authors: 182018 (English)In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 6, article id 130Article in journal (Refereed) Published
Abstract [en]

Accumulating evidence demonstrating higher cerebrospinal fluid (CSF) -synuclein (Syn) levels and Syn pathology in the brains of Alzheimer's disease (AD) patients suggests that Syn is involved in the pathophysiology of AD. To investigate whether Syn could be related to specific aspects of the pathophysiology present in both sporadic and familial disease, we quantified CSF levels of Syn and assessed links to various disease parameters in a longitudinally followed cohort (n=136) including patients with sporadic mild cognitive impairment (MCI) and AD, and in a cross-sectional sample from the Dominantly Inherited Alzheimer's Network (n=142) including participants carrying autosomal dominant AD (ADAD) gene mutations and their non-mutation carrying family members.Our results show that sporadic MCI patients that developed AD over a period of two years exhibited higher baseline Syn levels (p=0.03), which inversely correlated to their Mini-Mental State Examination scores, compared to cognitively normal controls (p=0.02). In the same patients, there was a dose-dependent positive association between CSF Syn and the APOE epsilon 4 allele. Further, CSF Syn levels were higher in symptomatic ADAD mutation carriers versus non-mutation carriers (p=0.03), and positively correlated to the estimated years from symptom onset (p=0.05) across all mutation carriers. In asymptomatic (Clinical Dementia Rating<0.5) PET amyloid-positive ADAD mutation carriers CSF Syn was positively correlated to C-11-Pittsburgh Compound-B (PiB) retention in several brain regions including the posterior cingulate, superior temporal and frontal cortical areas. Importantly, APOE epsilon 4-positive ADAD mutation carriers exhibited an association between CSF Syn levels and mean cortical PiB retention (p=0.032). In both the sporadic AD and ADAD cohorts we found several associations predominantly between CSF levels of Syn, tau and amyloid-(1-40).Our results suggest that higher CSF Syn levels are linked to AD pathophysiology at the early stages of disease development and to the onset of cognitive symptoms in both sporadic and autosomal dominant AD. We conclude that APOE epsilon 4 may promote the processes driven by Syn, which in turn may reflect on molecular mechanisms linked to the asymptomatic build-up of amyloid plaque burden in brain regions involved in the early stages of AD development.

Place, publisher, year, edition, pages
2018. Vol. 6, article id 130
Keywords [en]
Alzheimer's disease, Mild cognitive impairment, alpha-synuclein, Biomarkers, APOE epsilon 4
National Category
Geriatrics Neurosciences
Identifiers
URN: urn:nbn:se:su:diva-162760DOI: 10.1186/s40478-018-0624-zISI: 000451391000002PubMedID: 30477568OAI: oai:DiVA.org:su-162760DiVA, id: diva2:1274796
Available from: 2019-01-03 Created: 2019-01-03 Last updated: 2019-01-03Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Twohig, DanielPatra, KalicharanNielsen, Henrietta M.
By organisation
Department of Biochemistry and Biophysics
In the same journal
Acta neuropathologica communications
GeriatricsNeurosciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 52 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf