Alzheimer's disease is one of the main causes of cognitive impairment in the presenium and senium. Despite increased efforts in investigations of the aetiological background of the disease, most of the pathogenetic mechanisms remain unclear. From the morphological point of view, neurofibrillary degeneration and neuritic plaques, the main hallmarks of Alzheimer's disease, are mostly seen in the hippocampus and the cortex of the cerebral hemispheres. In contrast, the cerebellum and brain stem demonstrate minimal aggregates of neurofibrillary tangles. In addition, the neuronal population is better preserved in the cerebellum in contrast to the cortex of the brain hemispheres. In this study we attempted to detect alterations to the synapses in the vestibulocerebellar system, which is better preserved than the other structures in the central nervous system, even in the advanced stages of Alzheimer's disease. The morphological analysis is based on examination of 10 brains via electron microscopy and silver impregnation in the nodule, flocculus and vestibular nuclei. Morphological analysis revealed a limited number of neuritic plaques and minimal neurofibrillary tangles. However, synaptic alterations of the mossy fibres, granule cell dendrites, parallel fibres and Purkinje cell dendritic spines were extensively seen in Alzheimer's brains, in contrast to normal controls. In the granule layer, granule and Golgi cells were considerably decreased in number. The synapses between the mossy fibres and the granule cell dendrites were also decreased. Some of the synapses contained a limited number of polymorphous synaptic vesicles, numerous atypical mitochondria and dense bodies. Most synaptic alterations were in the mossy fibres' presynaptic terminals. The number of synaptic contacts between the mossy fibre terminals and the dendrites of the granule and Golgi cells was dramatically decreased. In the vestibular nuclei, substantial loss of synapses among the local neuronal circuits was also observed. Morphological alterations of the Golgi apparatus were seen in several neurons of the medial and lateral vestibular nuclei. In conclusion, these observations obviously plead in favour of a synaptic pathology among the primary pathogenetic processes in Alzheimer's.

Frontal dementia is a clinical entity of cognitive impairment, characterized mostly by progressive loss of fluency in speech, eventually resulting in aphasia or anomia, associated frequently with early loss of insight and many forms of inappropriate behavior. Hyperphosphorylation of the isoforms of tau protein, a microtubule-associated protein, which plays an important role in the pathogenetic mechanisms of Alzheimer's disease, is mainly involved in the pathogenesis of frontal dementia. In the present study, the morphological alterations of the acoustic cortex are described in three cases of dementia who fulfilled all the clinical and neuropathological criteria of frontal dementia. Specimens from the acoustic area of the temporal cortex were processed with Golgi silver impregnation techniques, Cajal and Rio Hortega stainings and electron microscopy. A tremendous loss of Cajal-Retzius neurons in layer I of the acoustic cortex was noticed in Golgi staining, associated with dense reactive astrocytosis, visualized clearly in Cajal gold impregnation technique. Loss of dendritic spines was extensively seen in layers III, V, and VI in correlation with normal controls. The electron microscopy revealed numerous Pick bodies, whose tau protein was the main protein constituent. Paired helical filaments were seen in the perikaryon and the axons of the neurons of layers IV, V, and VI. Synaptic alterations were extensively seen in the acoustic cortex consisting mainly of degeneration of the postsynaptic components. The authors think that the impressive morphological alterations of the acoustic cortex in frontal dementia might explain the early onset of deficiency of communication that most of the patients demonstrate in the initial stage of the disease.