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

• Published in: Brain research Vol. 1216; pp. 92 - 103
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 24-06-2008; Amsterdam Elsevier; New York, NY
• Subjects: Adult and adolescent clinical studies; Age Factors; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta; Amyloid beta-Peptides - metabolism; Amyloid Precursor Protein Secretases - metabolism; Animals; Beta-secretase; Biological and medical sciences; Brain - metabolism; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Gender difference; Hyperphosphorylation; Male; Medical sciences; Mice; Mice, Transgenic; Neprilysin; Neurology; Oligomer; Organic mental disorders. Neuropsychology; Presenilin-1 - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Sex Characteristics; Species Specificity; Tau; tau Proteins - metabolism; Transgenic mice; Hyperphosphorylation; Amyloid beta; Transgenic mice; Gender difference; Tau; Neprilysin; Beta-secretase; Oligomer; Alzheimer's disease; Alzheimer disease; Sex; Transgenic animal; Metalloendopeptidases; Female; Degenerative disease; Amyloid; Nervous system diseases; Enzyme; Rodentia; Cerebral disorder; Peptidases; Vertebrata; Anatomic pathology; Mammalia; Tau protein; Mouse; β Amyloid protein; Central nervous system disease; Hydrolases; Models
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.03.079

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.