LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease.
LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11 is markedly downregulated in patients with sporadic Alzheimer disease (AD). This finding led us to explore whether reduced LR11 expression reflects a primary mechanism of disease or merely a secondary consequence of other AD-associated changes. Therefore, LR11 expression was assessed in a transgenic mouse model of AD and familial AD (FAD) brains. Immunohistochemistry and immunoblotting of LR11 in PS1/APP transgenic and wild-type mice indicated that LR11 levels are not affected by genotype or accumulation of amyloid pathology. LR11 expression was also evaluated based on immunoblotting and LR11 immunostaining intensity in human frontal cortex in controls, sporadic AD, and FAD, including cases with presenilin-1 (PS1) and presenilin-2 (PS2) mutations. Although LR11 was reduced in sporadic AD, there was no difference in protein level or staining intensity between control and FAD cases. The finding that LR11 expression is unaffected in both a mouse model of AD and autosomal-dominant forms of AD suggests that LR11 is not regulated by amyloid accumulation or other AD neuropathologic changes. We hypothesize that LR11 loss may be specific to sporadic AD and influence amyloid pathology through mechanisms independent of substrate-enzyme interactions regulated by FAD mutations.
Dodson
Sara E
SE
Center for Neurodegenerative Disease, Department of Neurology, Emory University Atlanta, Georgia 30322, USA.
Gearing
Marla
M
Lippa
Carol F
CF
Montine
Thomas J
TJ
Levey
Allan I
AI
Lah
James J
JJ
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D026502:LDL-Receptor Related Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D053764:Presenilin-1; D011973:Receptors, LDL / Q000378:metabolism*
D000682:Amyloid; D026502:LDL-Receptor Related Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011973:Receptors, LDL; C102582:SORL1 protein, human