Stereotaxic injection of IgG from patients with Alzheimer disease initiates injury of cholinergic neurons of the basal forebrain.
BACKGROUND
The participation of an immune/inflammatory process in the pathomechanism of sporadic Alzheimer disease (AD) has been suggested by evidence for activated microglia and the potential therapeutic benefit of anti-inflammatory medication.


OBJECTIVE
To define a possible role for IgG in the immune/inflammatory process of AD in humans, we assayed the ability of IgG samples from patients with AD to target the injury to cholinergic neurons in rat basal forebrain in vivo.


METHODS
IgG purified from the serum or plasma from patients with AD and patients with other neurological disease who were used as control (DC) patients was injected stereotaxically into the medial septum of adult rats. Four weeks later coronal sections of the whole medial septum-diagonal bands of Broca region were immunostained for choline acetyltransferase (ChAT) to identify cholinergic neuronal cells.


METHODS
University medical centers.


METHODS
Blood samples were collected from 8 patients with probable and definite AD and from 6 age-matched DC patients.


METHODS
Detection of changes in the number of ChAT immunopositive cell profiles in sections and statistical evaluation.


RESULTS
Four weeks after the injections, IgG samples from patients with AD significantly reduced the number of ChAT-immunostained cell profiles in the whole medial septum-diagonal bands of Broca region compared with IgGs from DC patients. Neither DC IgGs nor saline solution significantly decreased the number of ChAT-immunopositive neuronal cell profiles.


CONCLUSIONS
Data document that IgG from patients with AD can target a stereotaxically induced immune/inflammatory injury to cholinergic neurons in the rat basal forebrain in vivo.
Engelhardt
J I
JI
Department of Neurology, Baylor College of Medicine, Houston, Tex 77030, USA.
Le
W D
WD
Siklós
L
L
Obál
I
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Boda
K
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Appel
S H
SH
D000544:Alzheimer Disease / Q000201:enzymology / Q000276:immunology*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D007267:Injections; D016548:Prosencephalon / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques
D007074:Immunoglobulin G; D002795:Choline O-Acetyltransferase