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  • Armstrong, AndreaLinköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet (author)

Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimers Disease

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2013-10-08
  • Humana Press,2014
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-105235
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-105235URI
  • https://doi.org/10.1007/s12017-013-8269-3DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The success of future intervention strategies for Alzheimers disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable biomarkers for AD are also needed in research and clinics for diagnosis, patient stratification, clinical trials, monitoring of disease progression and the development of new treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are among the first alterations observed in an AD brain. In this study, we performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were significantly increased in the CSF from AD patients compared with neurological controls. These results were confirmed in a validation cohort of CSF samples, and patients with no neurochemical evidence of AD, apart from increased total-tau, were found to have EEA1 levels corresponding to the increased total-tau levels. These findings indicate that increased levels of LAMP-1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased EEA1 levels may be a sign of general neurodegeneration. These six lysosomal network proteins are potential AD biomarkers and may be used to investigate lysosomal involvement in AD pathogenesis.

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  • Mattsson, NiklasSahlgrens University Hospital, Sweden University of Calif San Francisco, CA 94143 USA (author)
  • Appelqvist, HannaLinköpings universitet,Kemi,Tekniska högskolan(Swepub:liu)hanmi48 (author)
  • Janefjord, CamillaLinköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet(Swepub:liu)camja19 (author)
  • Sandin, LinneaLinköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet(Swepub:liu)linsa35 (author)
  • Agholme, LottaLinköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet(Swepub:liu)lothe38 (author)
  • Olsson, BobSahlgrens University Hospital, Sweden (author)
  • Svensson, SamuelLinköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Hälsouniversitetet,AlzeCure Fdn (author)
  • Blennow, KajSahlgrens University Hospital, Sweden (author)
  • Zetterberg, HenrikSahlgrens University Hospital, Sweden UCL Institute Neurol, England (author)
  • Kågedal, KatarinaLinköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet(Swepub:liu)katka10 (author)
  • Linköpings universitetAvdelningen för cellbiologi (creator_code:org_t)

Related titles

  • In:Neuromolecular medicine: Humana Press16:1, s. 150-1601535-10841559-1174

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