Beta-amyloid deposition and functional impairment in the retina of the APPswe/PS1DeltaE9 transgenic mouse model of Alzheimer's disease.
OBJECTIVE
To determine whether beta-amyloid (Abeta) deposition affects the structure and function of the retina of the APPswe/PS1DeltaE9 transgenic (tg) mouse model of Alzheimer's disease.


METHODS
Retinas from 12- to 19-month old APPswe/PS1DeltaE9 tg and age-matched non-transgenic (ntg) littermates were single or double stained with thioflavine-S and antibodies against Abeta, glial fibrillar acidic protein (GFAP), microglial marker F4/80, choline acetyltransferase (ChAT), and syntaxin 1. Quantification of thioflavine-S positive plaques and retinal layer thickness was analyzed semi-quantitatively, whereas microglial cell size and levels of F4/80 immunoreactivity were evaluated using a densitometry program. Scotopic electroretinogram (ERG) recording was used to investigate retinal physiology in these mice.


RESULTS
Thioflavine-S positive plaques appeared at 12 months in the retinas of APPswe/PS1DeltaE9 tg mice with the majority of plaques in the outer and inner plexiform layers. Plaques were embedded in the inner plexiform layer strata displaying syntaxin 1 and ChAT. The number and size of the plaques in the retina increased with age. Plaques appeared earlier and in greater numbers in females than in male tg littermate mice. Microglial activity was significantly increased in the retinas of APPswe/PS1DeltaE9 tg mice. Although we did not detect neuronal degeneration in the retina, ERG recordings revealed a significant reduction in the amplitudes of a- and b-waves in aged APPswe/PS1DeltaE9 tg compared to ntg littermates.


CONCLUSIONS
The present findings suggest that Abeta deposition disrupts retinal structure and may contribute to the visual deficits seen in aged APPswe/PS1DeltaE9 tg mice. Whether Abeta is involved in other forms of age-related retinal dysfunction is unclear.
Perez
Sylvia E
SE
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Lumayag
Stephen
S
Kovacs
Beatrix
B
Mufson
Elliott J
EJ
Xu
Shunbin
S
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D052160:Benzothiazoles; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D053764:Presenilin-1 / Q000235:genetics; D012160:Retina / Q000503:physiopathology; D012164:Retinal Diseases / Q000378:metabolism* / Q000503:physiopathology*; D050827:Syntaxin 1 / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000943:Antigens, Differentiation; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D053764:Presenilin-1; D050827:Syntaxin 1; D013844:Thiazoles; C036763:monocyte-macrophage differentiation antigen; C009462:thioflavin T; D002795:Choline O-Acetyltransferase
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