title: Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.
abstract: BACKGROUND
  Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).
  
  
  METHODS
  Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single-nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status.
  
  
  RESULTS
  Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344).
  
  
  CONCLUSIONS
  In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society.
authors: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Lynn M
authors: LM
authors: Bekris
authors: Northwest Network Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.|Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
authors: Debby W
authors: DW
authors: Tsuang
authors: Northwest Network Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.|Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
authors: Elaine R
authors: ER
authors: Peskind
authors: Geriatric Research, Education, and Clinical Center (GRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors: Chang E
authors: CE
authors: Yu
authors: Northwest Network Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.|Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.|Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.|Northwest Network Parkinson's Disease Research, Education and Clinical Center (PADRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.
authors: Thomas J
authors: TJ
authors: Montine
authors: Northwest Network Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.|Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.|Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.|Northwest Network Parkinson's Disease Research, Education and Clinical Center (PADRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.
authors: Jing
authors: J
authors: Zhang
authors: Geriatric Research, Education, and Clinical Center (GRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.|Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.|Northwest Network Parkinson's Disease Research, Education and Clinical Center (PADRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.
authors: Cyrus P
authors: CP
authors: Zabetian
authors: Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors: James B
authors: JB
authors: Leverenz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D020641:Polymorphism, Single Nucleotide
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases
keywords: ADAM10; APH1B; APP; BACE1; BACE2; NCSTN; PEN2; PSEN1; PSEN2; Parkinson's disease; cerebrospinal fluid