Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model

Chiho Hirata-Fukae, Hui Fang Li, Hyang Sook Hoe, Audrey J. Gray, S. Sakura Minami, Katsuyoshi Hamada, Takako Niikura, Fang Hua, Hiroe Tsukagoshi-Nagai, Yuko Horikoshi-Sakuraba, Mohamed Mughal, G. William Rebeck, Frank M. LaFerla, Mark P. Mattson, Nobuhisa Iwata, Takaomi C. Saido, William L. Klein, Karen E. Duff, Paul S. Aisen, Yasuji Matsuoka

Research output: Contribution to journalArticle

Abstract

Epidemiological studies indicate that women have a higher risk of Alzheimer's disease (AD) even after adjustment for age. Though transgenic mouse models of AD develop AD-related amyloid beta (Abeta) and/or tau pathology, gender differences have not been well documented in these models. In this study, we found that female 3xTg-AD transgenic mice expressing mutant APP, presenilin-1 and tau have significantly more aggressive Abeta pathology. We also found an increase in beta-secretase activity and a reduction of neprilysin in female mice compared to males; this suggests that a combination of increased Abeta production and decreased Abeta degradation may contribute to higher risk of AD in females. In contrast to significantly more aggressive Abeta pathology in females, gender did not affect the levels of phosphorylated tau in 3xTg-AD mice. These results point to the involvement of Abeta pathways in the higher risk of AD in women. In addition to comparison of pathology between genders at 9, 16 and 23 months of age, we examined the progression of Abeta pathology at additional age points; i.e., brain Abeta load, intraneuronal oligomeric Abeta distribution and plaque load, in male 3xTg-AD mice at 3, 6, 9, 12, 16, 20 and 23 months of age. These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research.

Original languageEnglish (US)
Pages (from-to)92-103
Number of pages12
JournalBrain Research
Volume1216
DOIs
StatePublished - Jun 24 2008
Externally publishedYes

Fingerprint

Amyloid
Alzheimer Disease
Pathology
Transgenic Mice
Presenilin-1
Therapeutic Human Experimentation
Neprilysin
Amyloid Precursor Protein Secretases
Epidemiologic Studies
Brain

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Beta-secretase
  • Gender difference
  • Hyperphosphorylation
  • Neprilysin
  • Oligomer
  • Tau
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Hirata-Fukae, C., Li, H. F., Hoe, H. S., Gray, A. J., Minami, S. S., Hamada, K., ... Matsuoka, Y. (2008). Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Research, 1216, 92-103. https://doi.org/10.1016/j.brainres.2008.03.079

Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. / Hirata-Fukae, Chiho; Li, Hui Fang; Hoe, Hyang Sook; Gray, Audrey J.; Minami, S. Sakura; Hamada, Katsuyoshi; Niikura, Takako; Hua, Fang; Tsukagoshi-Nagai, Hiroe; Horikoshi-Sakuraba, Yuko; Mughal, Mohamed; Rebeck, G. William; LaFerla, Frank M.; Mattson, Mark P.; Iwata, Nobuhisa; Saido, Takaomi C.; Klein, William L.; Duff, Karen E.; Aisen, Paul S.; Matsuoka, Yasuji.

In: Brain Research, Vol. 1216, 24.06.2008, p. 92-103.

Research output: Contribution to journalArticle

Hirata-Fukae, C, Li, HF, Hoe, HS, Gray, AJ, Minami, SS, Hamada, K, Niikura, T, Hua, F, Tsukagoshi-Nagai, H, Horikoshi-Sakuraba, Y, Mughal, M, Rebeck, GW, LaFerla, FM, Mattson, MP, Iwata, N, Saido, TC, Klein, WL, Duff, KE, Aisen, PS & Matsuoka, Y 2008, 'Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model', Brain Research, vol. 1216, pp. 92-103. https://doi.org/10.1016/j.brainres.2008.03.079
Hirata-Fukae, Chiho ; Li, Hui Fang ; Hoe, Hyang Sook ; Gray, Audrey J. ; Minami, S. Sakura ; Hamada, Katsuyoshi ; Niikura, Takako ; Hua, Fang ; Tsukagoshi-Nagai, Hiroe ; Horikoshi-Sakuraba, Yuko ; Mughal, Mohamed ; Rebeck, G. William ; LaFerla, Frank M. ; Mattson, Mark P. ; Iwata, Nobuhisa ; Saido, Takaomi C. ; Klein, William L. ; Duff, Karen E. ; Aisen, Paul S. ; Matsuoka, Yasuji. / Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. In: Brain Research. 2008 ; Vol. 1216. pp. 92-103.
@article{08329b8df4fc4ff39618c156d15a0d17,
title = "Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model",
abstract = "Epidemiological studies indicate that women have a higher risk of Alzheimer's disease (AD) even after adjustment for age. Though transgenic mouse models of AD develop AD-related amyloid beta (Abeta) and/or tau pathology, gender differences have not been well documented in these models. In this study, we found that female 3xTg-AD transgenic mice expressing mutant APP, presenilin-1 and tau have significantly more aggressive Abeta pathology. We also found an increase in beta-secretase activity and a reduction of neprilysin in female mice compared to males; this suggests that a combination of increased Abeta production and decreased Abeta degradation may contribute to higher risk of AD in females. In contrast to significantly more aggressive Abeta pathology in females, gender did not affect the levels of phosphorylated tau in 3xTg-AD mice. These results point to the involvement of Abeta pathways in the higher risk of AD in women. In addition to comparison of pathology between genders at 9, 16 and 23 months of age, we examined the progression of Abeta pathology at additional age points; i.e., brain Abeta load, intraneuronal oligomeric Abeta distribution and plaque load, in male 3xTg-AD mice at 3, 6, 9, 12, 16, 20 and 23 months of age. These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research.",
keywords = "Alzheimer's disease, Amyloid beta, Beta-secretase, Gender difference, Hyperphosphorylation, Neprilysin, Oligomer, Tau, Transgenic mice",
author = "Chiho Hirata-Fukae and Li, {Hui Fang} and Hoe, {Hyang Sook} and Gray, {Audrey J.} and Minami, {S. Sakura} and Katsuyoshi Hamada and Takako Niikura and Fang Hua and Hiroe Tsukagoshi-Nagai and Yuko Horikoshi-Sakuraba and Mohamed Mughal and Rebeck, {G. William} and LaFerla, {Frank M.} and Mattson, {Mark P.} and Nobuhisa Iwata and Saido, {Takaomi C.} and Klein, {William L.} and Duff, {Karen E.} and Aisen, {Paul S.} and Yasuji Matsuoka",
year = "2008",
month = "6",
day = "24",
doi = "10.1016/j.brainres.2008.03.079",
language = "English (US)",
volume = "1216",
pages = "92--103",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model

AU - Hirata-Fukae, Chiho

AU - Li, Hui Fang

AU - Hoe, Hyang Sook

AU - Gray, Audrey J.

AU - Minami, S. Sakura

AU - Hamada, Katsuyoshi

AU - Niikura, Takako

AU - Hua, Fang

AU - Tsukagoshi-Nagai, Hiroe

AU - Horikoshi-Sakuraba, Yuko

AU - Mughal, Mohamed

AU - Rebeck, G. William

AU - LaFerla, Frank M.

AU - Mattson, Mark P.

AU - Iwata, Nobuhisa

AU - Saido, Takaomi C.

AU - Klein, William L.

AU - Duff, Karen E.

AU - Aisen, Paul S.

AU - Matsuoka, Yasuji

PY - 2008/6/24

Y1 - 2008/6/24

N2 - Epidemiological studies indicate that women have a higher risk of Alzheimer's disease (AD) even after adjustment for age. Though transgenic mouse models of AD develop AD-related amyloid beta (Abeta) and/or tau pathology, gender differences have not been well documented in these models. In this study, we found that female 3xTg-AD transgenic mice expressing mutant APP, presenilin-1 and tau have significantly more aggressive Abeta pathology. We also found an increase in beta-secretase activity and a reduction of neprilysin in female mice compared to males; this suggests that a combination of increased Abeta production and decreased Abeta degradation may contribute to higher risk of AD in females. In contrast to significantly more aggressive Abeta pathology in females, gender did not affect the levels of phosphorylated tau in 3xTg-AD mice. These results point to the involvement of Abeta pathways in the higher risk of AD in women. In addition to comparison of pathology between genders at 9, 16 and 23 months of age, we examined the progression of Abeta pathology at additional age points; i.e., brain Abeta load, intraneuronal oligomeric Abeta distribution and plaque load, in male 3xTg-AD mice at 3, 6, 9, 12, 16, 20 and 23 months of age. These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research.

AB - Epidemiological studies indicate that women have a higher risk of Alzheimer's disease (AD) even after adjustment for age. Though transgenic mouse models of AD develop AD-related amyloid beta (Abeta) and/or tau pathology, gender differences have not been well documented in these models. In this study, we found that female 3xTg-AD transgenic mice expressing mutant APP, presenilin-1 and tau have significantly more aggressive Abeta pathology. We also found an increase in beta-secretase activity and a reduction of neprilysin in female mice compared to males; this suggests that a combination of increased Abeta production and decreased Abeta degradation may contribute to higher risk of AD in females. In contrast to significantly more aggressive Abeta pathology in females, gender did not affect the levels of phosphorylated tau in 3xTg-AD mice. These results point to the involvement of Abeta pathways in the higher risk of AD in women. In addition to comparison of pathology between genders at 9, 16 and 23 months of age, we examined the progression of Abeta pathology at additional age points; i.e., brain Abeta load, intraneuronal oligomeric Abeta distribution and plaque load, in male 3xTg-AD mice at 3, 6, 9, 12, 16, 20 and 23 months of age. These findings confirm progressive Abeta pathology in 3xTg-AD transgenic mice, and provide guidance for their use in therapeutic research.

KW - Alzheimer's disease

KW - Amyloid beta

KW - Beta-secretase

KW - Gender difference

KW - Hyperphosphorylation

KW - Neprilysin

KW - Oligomer

KW - Tau

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=44949210283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44949210283&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2008.03.079

DO - 10.1016/j.brainres.2008.03.079

M3 - Article

C2 - 18486110

AN - SCOPUS:44949210283

VL - 1216

SP - 92

EP - 103

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -