Purkinje cell loss and astrocytosis in the cerebellum in familial and sporadic Alzheimer's disease

Background/Aims: Previous studies used 192 IgG-saporin to study cholinergic function because of its facility for selective lesioning; however, results varied due to differences in the methods of administration and behavioral tests used. We examined an animal model of dementia using 192 IgG-saporin to confirm its features before applying this model to research of therapeutic drugs or electrical stimulation techniques. Methods: Features were verified by the Morris water maze test, immunochemistry, and Western blotting. Animals were examined after intraventricular injection of 192 IgG-saporin (0.63 µg/µl; 6, 8, and 10 µl) or phosphate-buffered saline. Results: In the acquisition phase of the Morris water maze test, the latencies of the injection groups were significantly delayed, but recovered within 1 week. In the probe test, 2 of 4 indices (time in the platform zone and the number of crossings) were significantly different in the 8-µl injection group. Immunohistochemistry revealed the extent of cholinergic destruction. Activity-regulated cytoskeleton-associated protein and glutamate decarboxylase expression significantly decreased in the frontal cortex (8- and 10-µl groups), but not in the hippocampus. Conclusion: Spatial memory impairment was associated with cholinergic basal forebrain injury as well as frontocortical GABAergic hypofunction and synaptic plasticity deceleration.

Section: Discussionmentioning

confidence: 99%

Decrease of GABAergic Markers and Arc Protein Expression in the Frontal Cortex by Intraventricular 192 IgG-Saporin

Jeong¹,

Chang²,

Hwang³

et al. 2011

“…However, the randomness of Golgi labelling makes such a study hard to evaluate, and a more recent immunocytochemical study reported no structural abnormalities in Purkinje cells despite frequent physical contact between their dendrites and diffuse amyloid deposits [15]. Recently, a reduction in Purkinje cell density in the cerebellum in both familial and sporadic AD has been reported, which shows an inverse correlation with astrocyte density [38], The absence of tau-immunoreactive PHF in AD cere bellum initially prompted the conclusion that cerebellar amyloid is never associated with neuritic change [10], However, since PHF and tau antigens may not be obliga tory components of abnormal neurites in AD neocortex [33], this observation does not exclude the possibility that abnormal neurites may be present in AD cerebellum. Experimental evidence supporting this includes the ob servation of swollen neuritic processes in association with cerebellar plaques using the Holmes silver stain for axons [4], More recently, immunoelectron microscopy [39] and modified Bielschowsky and immunocytochemical tech niques [40] have shown ubiquilin-positive granular ele ments containing membranous and vesicular dense bod ies which resemble dystrophic neurites in association with many cerebellar plaques.…”

Section: Dendrites Neurites and Synapsesmentioning

confidence: 99%

The Cerebellum in Alzheimer's Disease

Larner

1997

118

The cerebellum is a relatively neglected area of the Alzheimer''s disease (AD) brain, probably because it was formerly thought to be spared by the disease. However, a number of pathological changes have now been revealed in the AD cerebellum, principally by immunocytochemical studies, including widespread deposits of diffuse amyloid, ubiquitin-immunoreactive dystrophic neurites, and increased microglia, but tau-immunoreactive neurofibrillary tangles have not been seen. Although the observed changes may be merely epiphenomenal to the pathological processes occurring in the AD neocortex and hippocampus, the morphological and immunocytochemical differences between AD cerebral cortex and cerebellar cortex may nonetheless give insights into the molecular factors involved in the development of the neuro-pathological lesions of AD brain.

“…Morphological studies on the cerebellum in AD have concentrated on the traditional neuropathological (NP) hallmarks of AD, such as amyloid plaques, neurofibrillary tangles [9,10] and amyloid angiopathy [11], but less is reported on neuronal loss and other structural changes in AD [12][13][14]. The cerebellum shows a neuronal cell loss with characteristic regional differences following hypoxia, abuse of ethyl [15][16][17] and also as a consequence of normal aging [18,19], but is only rarely mentioned to harbor particular pathological changes in AD [9,12,13,20].…”

Section: Introductionmentioning

confidence: 99%

Alzheimer’s Disease and the Cerebellum: A Morphologic Study on Neuronal and Glial Changes

Sjöbeck

Englund²

2001

Structural manifestations of Alzheimer’s disease (AD) including neuronal loss were investigated in 12 cases of AD and in 10 healthy age-matched controls, with focus on the cerebellum. Linear Purkinje cell (PC) density was measured in the vermis and cerebellar hemispheres. Neurons were also counted in the inferior olivary nucleus. In vermis of the AD cases, the mean PC number was significantly lower (p = 0.019) than in the controls. The neurons in the inferior olive were similarly fewer, though not significantly (p = 0.13). Molecular layer gliosis and atrophy in the vermis was clearly severer in AD than in the controls. Features typical of cerebral Alzheimer encephalopathy (plaques, tangles and microvacuolization) were inconspicious. The structural cerebellar changes in the AD cases were thus neuronal loss, atrophy and gliosis, judged to represent the disease process, and with a main involvement in the vermis. This may be reflected in some of the symptoms and signs seen in AD, signs that are generally overlooked or judged to be of noncerebellar origin.