Abstract
Alzheimer’s disease (AD) is characterized by a decline of cognitive functions. Distinctive histopathological hallmarks are neuritic plaques, neurofibrillary tangles, and synaptic alterations. Abnormally enlarged synaptic structures called “Meganeurite clusters” have been linked to plasticity changes. The aims of this study were to determine if cognitive impairment was related to specific neuritic and synaptic degeneration processes in patients with AD, and if the results of a cognitive test could be correlated with the histopathological damage. The neuropsychological evaluation obtained by the Protocole d’evaluation neuropsychologique optimal (PENO) test battery was used in live AD and control individuals. The histopathological evaluation of their brain after their death was carried out with specific polyclonal and monoclonal antibodies to Aβ, pTau protein, synaptophysin, and GAP-43. Images were obtained by confocal microscopy. The results showed a significant difference between healthy controls and Alzheimer’s patients in neuropsychological evaluation and histopathological hallmarks expression. The most significant positive correlation in AD patients was between memory and language results with the PENO test and the presence of Aβ +pTau+ plaques in the hippocampus. An interesting negative correlation was between cognitive impairment and the presence of Meganeuritic clusters, considered as “plasticity” markers. These results strongly supported the use of the PENO battery test to evaluate the progression of cognitive impairment in AD prone individuals and patients due to the strong correlation of the test results with histopathological brain lesions characteristic of Alzheimer’s disease.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative and multifactorial illness [1]
The Protocole d’evaluation neuropsychologique optimal (PENO) test battery [5] permits a superior neuropsychological evaluation in the progression of dementia; this test brings to the fore distinct affected cognitive profiles in a transversal as well as longitudinal base, contributing to the early diagnosis of AD as it can differentiate between normal and pathological aging
AD is characterized by the appearance of parenchymal amyloid-β deposits with and without neuritic elements, and by intraneuronal changes, including neurofibrillary tangles (NFTs) and synaptic loss [6]
Summary
The clinical symptoms involve cognitive impairment in different areas, mainly: memory, language, viso-constructive, spatial attention, praxis, gnosis, and executive functions [2]. The Protocole d’evaluation neuropsychologique optimal (PENO) test battery [5] permits a superior neuropsychological evaluation in the progression of dementia; this test brings to the fore distinct affected cognitive profiles (memory, language, praxis, gnosis and executive functions) in a transversal as well as longitudinal base, contributing to the early diagnosis of AD as it can differentiate between normal and pathological aging. AD is characterized by the appearance of parenchymal amyloid-β deposits with and without neuritic elements, and by intraneuronal changes, including neurofibrillary tangles (NFTs) and synaptic loss [6]. Neuritic plaques comprise amyloid-β deposits surrounded by dystrophic neurites, reactive astrocytes, and microglia [7] [8]. Neurodegeneration in AD brains co-exists with a reactive plasticity event because Amyloid-β Deposits (AβDs), classic Neuritic Plaques (NPs), and Dystrophic Neurites Clusters lacking amyloid-β deposits (DNCs), all of which represent structures associated to the neuritic degenerative process, are co-located with reactive plasticity structures called Meganeuritic Clusters (MCs) and peri-neuronal sprouting in neurons of the hippocampus, which are strongly positive for synaptophysin and GAP-43 [11] [12]
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