title: Cholinergic dysfunction in diseases with Lewy bodies.
abstract: OBJECTIVE
  To evaluate cholinergic activity in diseases with Lewy bodies (LB; LB variant of AD [LBV], diffuse LB disease [DLBD], and Parkinson's disease [PD]) to determine if 1) AD changes are requisite to cholinergic dysfunction, 2) cholinergic activity declines to the same extent in neocortical and archicortical areas, and 3) cholinergic loss is influenced by APOE genotype.
  
  
  BACKGROUND
  Like AD, diseases with LB are associated with decreased choline acetyltransferase (ChAT) activity. Increased APOE epsilon4 allele frequency has been reported in LBV. Whether APOE genotype affects cholinergic function in LBV remains unclear.
  
  
  METHODS
  An autopsy series of 182 AD (National Institute on Aging and Consortium to Establish a Registry for Alzheimer's Disease criteria), 49 LBV, 11 PD, 6 DLBD, and 16 normal control (NC) subjects. APOE genotype and ChAT activity (nmol/h/100 mg) in the midfrontal and hippocampal cortices were determined.
  
  
  RESULTS
  Mean midfrontal ChAT activity was markedly reduced in diseases with LB (LBV: 53.3 +/- 39.0; PD: 54.8 +/- 35.7; DLBD: 41.3 +/- 24.8) compared to NC (255.4 +/- 134.6; p < 0.001) and AD (122.6 +/- 78.9; p < 0.05). Among diseases with LB, midfrontal ChAT activity was decreased to a similar extent in patients with (LBV) and without (DLBD and PD) AD pathology. Although mean ChAT activity for LBV was less than half that for AD in the midfrontal cortex, it was similar to that for AD in the hippocampus (LBV: 243.5 +/- 189.7; AD: 322.8 +/- 265.6; p > 0.05). However, hippocampal ChAT activity for both AD and LBV was lower than that for NC (666.5 +/- 360.3; p < 0.001). The epsilon4 allele dosage did not influence midfrontal ChAT activity in LBV.
  
  
  CONCLUSIONS
  Marked losses in midfrontal ChAT activity occur in diseases with LB, independent of coexistent AD changes. A greater midfrontal, as opposed to hippocampal, cholinergic deficit may differentiate LBV from AD. The lack of a relationship between epsilon4 allele dosage and midfrontal ChAT activity suggests that other factors may play a role in its decline in LBV.
authors.affiliation: Neurologia Prima, Ospediali Riuniti, Bergamo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Tiraboschi
authors.forename: L A
authors.initials: LA
authors.lastname: Hansen
authors.forename: M
authors.initials: M
authors.lastname: Alford
authors.forename: M N
authors.initials: MN
authors.lastname: Sabbagh
authors.forename: B
authors.initials: B
authors.lastname: Schoos
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.forename: L J
authors.initials: LJ
authors.lastname: Thal
authors.forename: J
authors.initials: J
authors.lastname: Corey-Bloom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000201:enzymology* / Q000473:pathology; D005625:Frontal Lobe / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D005838:Genotype; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics / Q000503:physiopathology*; D008875:Middle Aged
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002795:Choline O-Acetyltransferase