C. Schultz

The deposition of Abeta protein (Abeta) and the development of neurofibrillary changes are important histopathological hallmarks of Alzheimer disease (AD). In this study, the medial temporal lobe serves as a model for the changes in the anatomical distribution pattern of different types of Abeta-deposits occurring in the course of AD, as well as for the relationship between the development of Abeta-deposition and that of neurofibrillary pathology. In the first of 4 phases of beta-amyloidosis, diffuse non-neuritic plaques are deposited in the basal temporal neocortex. The same plaque type appears in the second phase within the external entorhinal layers pre-beta and pre-gamma, and fleecy amyloid deposits occur in the internal entorhinal layers pri-alpha, pri-beta, pri-gamma, and in CA1. In the third phase, Abeta-deposits emerge in the molecular layer of the fascia dentata, and band-like Abeta-deposits occur in the subpial portion of the molecular layer of both the entorhinal region and the temporal neocortex. In addition, confluent lake-like Abeta-deposits appear in the parvopyramidal layer of the presubicular region. The fourth phase is characterized by diffuse and core-only plaques in CA4. Diffuse plaques evolve sporadically in the external entorhinal layer pre-alpha. Parallel to the evolution of beta-amyloidosis as represented by the 4 phases, neuritic plaques gradually make their appearance in the temporal neocortex, entorhinal region, CA1, the molecular layer of the fascia dentata, and CA4. A prerequisite for their development is the presence of Abeta and the presence of neurofibrillary tangles in neurons targeting the regions where neuritic plaques evolve. Each of the different types of Abeta-deposits, including neuritic plaques, plays a specific role in the distinct developmental sequence as represented by the 4 phases so that the medial temporal lobe inexorably becomes involved to an ever greater extent. The step-for-step involvement of connected anatomical subfields highlights the importance of the entorhino-hippocampal pathways for the expansion of beta-amyloidosis. The 4 phases in the evolution of beta-amyloidosis correlate significantly with the stages of the neurofibrillary pathology proposed by Braak and Braak.

This article reviews data on the internal organization, neuronal types, and interconnections of limbic and motor components of the human brain, and the specific lesions which a few of them undergo during the course of Parkinson's disease (neuronal loss associated with the development of Lewy bodies and Lewy neurites). The severe involvement of nigral neuromelanin-laden projection cells has received particular attention during the past decades. This lesion interferes with normal function of the striatum and probably contributes to many of the motor dysfunctions characteristically occurring in Parkinson's disease. The similarly severe involvement of several areas and nuclei outside of the substantia nigra has often escaped notice. However, the pathology of Parkinson's disease cannot be completely described unless changes in these extranigral areas are taken into account. Interpretation of the characteristic lesional pattern is facilitated by combining schemata of both the limbic and motor systems. This approach reveals a key role by the amygdala and related structures in extranigral pathology. Severe lesions occur in the central amygdaloid nucleus, in nuclei projecting to the cerebral cortex in a non-specific manner, and in nuclei regulating endocrine and autonomic functions. It is suggested that extranigral lesions contribute to the development of behavioral changes and autonomic dysfunction.

The formation of amyloid plaques is a hallmark of Alzheimer's disease (AD). Amyloid plaques and vascular amyloid deposits in cerebral amyloid angiopathy (CAA) consist of the beta-amyloid protein (Abeta) in association with other proteins. These Abeta-deposits can be visualized by thioflavin S, Congo red staining, silver staining methods and immunohistochemistry. Senile plaques also have been shown to exhibit blue autofluorescence. Here we report that UV light-induced autofluorescence is restricted to full-length Abeta-containing amyloid plaques and is also seen in blood vessels affected by CAA. Different types of samples from AD and control cortices were examined: native samples, formalin-fixed paraffin and polyethylene glycol-embedded tissue sections. These samples were viewed with a fluorescence microscope under UV light excitation (360 - 370 nm). By emitting blue fluorescence (>420 nm), amyloid plaques and blood vessels affected by CAA were detected in AD and CAA samples. Combination with immunofluorescence against anti-Abeta1-42, anti-Abeta17-24, and anti-Abeta8-17 demonstrated co-localization of the autofluorescent deposits with full-length Abeta containing Abeta-deposits. N-terminal truncated Abeta-deposits, such as the fleecy amyloid, do not exhibit autofluorescence. In doing so, Abeta-autofluorescence is a suitable method for screening native tissue samples for full-length Abeta-deposits. In contradistinction to conventional and immunohistochemical procedures, detection of plaques and CAA by autofluorescence enables the recognition of full-length Abeta-deposits in the human brain without any chemical interaction whatsoever on the part of Abeta.