Apolipoprotein D levels are elevated in prefrontal cortex of subjects with Alzheimer's disease: no relation to apolipoprotein E expression or genotype.
BACKGROUND
Apolipoprotein E (apoE) has been implicated in the pathology of AD ever since inheritance of the epsilon4 allele was shown to be an important risk factor for the development of AD. Apolipoprotein D (apoD) is elevated in association with several central nervous system disorders, including Alzheimer's disease (AD), and has been proposed to be an especially robust marker for brain regions specifically affected by particular neuropathologies. Progressive cognitive decline is the core clinical feature of AD and is associated with disturbances in the prefrontal cortex.


METHODS
We measured apoD levels in prefrontal cortex samples obtained postmortem from 20 autopsy-confirmed AD subjects and 40 control subjects.


RESULTS
Enzyme-linked immunosorbent assay analysis revealed a significant increase in apoD expression in AD subjects compared with control subjects (.218+/-.029 microg/mg protein vs.117+/-.011 microg/mg protein; p=0003). There was no significant difference in apoD expression between early-onset and late-onset Alzheimer's subjects. Apolipoprotein D expression levels were not correlated with apoE levels, nor were they correlated with inheritance of the APOE epsilon4 allele.


CONCLUSIONS
These findings suggest that apoD may be related to the cognitive decline observed in AD patients and that apoD and apoE likely play different roles in the pathogenesis of AD.
Thomas
Elizabeth A
EA
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Laws
Simon M
SM
Sutcliffe
J Gregor
JG
Harper
Clive
C
Dean
Brian
B
McClean
Catriona
C
Masters
Colin
C
Lautenschlager
Nicola
N
Gandy
Samuel E
SE
Martins
Ralph N
RN
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000378:metabolism*; D001053:Apolipoproteins / Q000378:metabolism*; D053399:Apolipoproteins D; D001057:Apolipoproteins E / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D015854:Up-Regulation
D001053:Apolipoproteins; D053399:Apolipoproteins D; D001057:Apolipoproteins E; D015415:Biomarkers