title: Amyloid cascade and tau pathology cerebrospinal fluid markers in mild cognitive impairment with regards to Alzheimer's disease cerebral metabolic signature.
abstract: BACKGROUND
  Biomarker relationships in early stages of Alzheimer's disease (AD) are elusive. Cerebrospinal fluid (CSF) levels of amyloid-β 1-42 (Aβ42) and total tau (tTau) as well as 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) contribute to help unravel AD pathology. Furthermore, peptides related to amyloid-β protein precursor (AβPP) processing [e.g., soluble AβPPα and β (sAβPPα and sAβPPβ, respectively); sortilin-related receptor with A-type repeats (SORL1, also called LR11 or SORLA)] are factors crucially implicated in the formation of pathological hallmarks of AD.
  
  
  OBJECTIVE
  To unveil differences in CSF concentrations of Aβ42, sAβPPα, sAβPPβ, tTau, and SORL1 between patients with mild cognitive impairment (MCI) who were categorized according to expert interpretation of FDG scans.
  
  
  METHODS
  PET results were classified as suggesting high likelihood for AD (MCI-AD high), intermediate likelihood for AD (MCI-AD intermediate), or little likelihood for AD (MCI-AD unlikely). An AD dementia group was also included. Differences between the groups were tested by Kruskal- Wallis test, Mann-Whitney test, or χ2. Provided statistically significant differences were detected, multiple linear regression models were employed.
  
  
  RESULTS
  Aβ42 levels in patients with MCI-AD high (n = 15) were lower compared to MCI-AD intermediate (n = 18) and MCI-AD unlikely patients (n = 25) (p = 0.002), while they did not differ from patients with AD dementia (n = 17). The regression model revealed a significant impact of the metabolic pattern on Aβ42 concentrations. SORL1, tTau, sAβPPα, and sAβPPβ concentrations did not differ between the groups.
  
  
  CONCLUSIONS
  These findings point to linkages between plaque pathology and glucose cerebral hypometabolism.
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. panos.alexopoulos@lrz.tum.de
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.forename: Liang-Hao
authors.initials: LH
authors.lastname: Guo
authors.forename: Meizi
authors.initials: M
authors.lastname: Jiang
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.forename: Stefan
authors.initials: S
authors.lastname: Förster
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000134:cerebrospinal fluid; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D019788:Fluorodeoxyglucose F18; D010446:Peptide Fragments; D016875:tau Proteins; D000099183:Sortilin; C075222:amyloid beta-protein (1-42)