title: Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice.
abstract: Intraneuronal alpha-synuclein (alphaSYN) inclusions constitute the hallmark lesions of a number of neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies. In a transgenic mouse model expressing mutant [A30P]alphaSYN under control of the pan-neuronal Thy1 promoter, motor impairment became significant beyond 17 months of age. Cognitive performance was measured in the Morris water maze and upon fear conditioning. At 4 months of age, transgenic mice performed like controls. However, performance in these tasks was significantly impaired in (Thy1)-h[A30P]alphaSYN mice at 12 months of age. After completion of the cognition tests, mice were sacrificed and the regional distribution of neuropathology was examined. In contrast to 4 months old animals, 12 months old transgenic mice showed alpha-synucleinopathy in several brain regions, including the central nucleus of the amygdala, which is involved in cognitive behavior of mice, and is susceptible to alphaSYN pathology in human patients. Thus, age-dependent fibrillization of alphaSYN in specific cortical regions concomitant with cognitive decline may reflect dementia with Lewy bodies in a transgenic mouse model.
authors.affiliation: Pharma Research, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Freichel
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: Theresa
authors.initials: T
authors.lastname: Ballard
authors.forename: Veronika
authors.initials: V
authors.lastname: Müller
authors.forename: Marie
authors.initials: M
authors.lastname: Woolley
authors.forename: Laurence
authors.initials: L
authors.lastname: Ozmen
authors.forename: Edilio
authors.initials: E
authors.lastname: Borroni
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: Will
authors.initials: W
authors.lastname: Spooren
authors.forename: Philipp J
authors.initials: PJ
authors.lastname: Kahle
mesh_terms: D000367:Age Factors; D000679:Amygdala / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D019286:Endopeptidase K / Q000378:metabolism; D005239:Fear; D017403:In Situ Hybridization; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology; D009460:Neurologic Examination; D011597:Psychomotor Performance; D045442:Rotarod Performance Test; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D019286:Endopeptidase K