Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.

Recent human trials of treatments for Alzheimer's disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whethe...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Amanda L Wright, Raphael Zinn, Barbara Hohensinn, Lyndsey M Konen, Sarah B Beynon, Richard P Tan, Ian A Clark, Andrea Abdipranoto, Bryce Vissel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa2d2c1613f94623aac0a56d33b91559
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:aa2d2c1613f94623aac0a56d33b91559
record_format	dspace
spelling	oai:doaj.org-article:aa2d2c1613f94623aac0a56d33b915592021-11-18T07:51:15ZNeuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.1932-620310.1371/journal.pone.0059586https://doaj.org/article/aa2d2c1613f94623aac0a56d33b915592013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23560052/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recent human trials of treatments for Alzheimer's disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-βAβ? plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression.Amanda L WrightRaphael ZinnBarbara HohensinnLyndsey M KonenSarah B BeynonRichard P TanIan A ClarkAndrea AbdipranotoBryce VisselPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e59586 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amanda L Wright Raphael Zinn Barbara Hohensinn Lyndsey M Konen Sarah B Beynon Richard P Tan Ian A Clark Andrea Abdipranoto Bryce Vissel Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.
description	Recent human trials of treatments for Alzheimer's disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-βAβ? plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression.
format	article
author	Amanda L Wright Raphael Zinn Barbara Hohensinn Lyndsey M Konen Sarah B Beynon Richard P Tan Ian A Clark Andrea Abdipranoto Bryce Vissel
author_facet	Amanda L Wright Raphael Zinn Barbara Hohensinn Lyndsey M Konen Sarah B Beynon Richard P Tan Ian A Clark Andrea Abdipranoto Bryce Vissel
author_sort	Amanda L Wright
title	Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.
title_short	Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.
title_full	Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.
title_fullStr	Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.
title_full_unstemmed	Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.
title_sort	neuroinflammation and neuronal loss precede aβ plaque deposition in the happ-j20 mouse model of alzheimer's disease.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/aa2d2c1613f94623aac0a56d33b91559
work_keys_str_mv	AT amandalwright neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT raphaelzinn neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT barbarahohensinn neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT lyndseymkonen neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT sarahbbeynon neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT richardptan neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT ianaclark neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT andreaabdipranoto neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease AT brycevissel neuroinflammationandneuronallossprecedeabplaquedepositioninthehappj20mousemodelofalzheimersdisease
_version_	1718422872408457216

Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.

Ejemplares similares