Démence vasculaire : les grands effets des petites lésions

Vascular dementia due to multiple large strokes (multi-infarct dementia) is a well known entity. However, new clinicopathologic and neuroimaging data have highlighted the common occurrence of small vessel and microscopic vascular pathology in aging brains and recognized that vascular dementia due to small lesions is probably the most common form. In such cases, cortical microinfarcts are the strongest correlate of global cognitive function followed by basal ganglia and thalamic lacunes. Demyelination is only weekly associated with cognition and this relation is no longer significant after adjustement for the presence of lacunes. Awareness of the importance of small vascular lesions in brain aging, can improve diagnostic accuracy and help identify new targets, that could lead to novel therapeutic approaches in old age dementia

Neuropathology of Lewy body disorders

The spectrum of Lewy body disorders includes not only Parkinson's disease, dementia with Lewy bodies and Parkinson's disease associated dementia but also Lewy body dysphagia and autonomic failure with Lewy bodies. In the last years an increasing number of cases showing Lewy body pathology has been recognised at autopsy. In fact, dementia with Lewy bodies is thought to be the second most frequent degenerative cause of cognitive decline in elderly after Alzheimer's disease, representing about 20% of dementia cases. The clinical diagnosis of dementia with Lewy bodies and of Parkinson's disease dementia is determinant for prognosis and therapeutic management, namely for avoiding increased sensibility to neuroleptics. The recent progress of neuropathology in this field made it possible to define clinical and neuropathological guidelines for the diagnosis. This review briefly describes the most important data of all Lewy body related disorders

Maladie d'Alzheimer: de la pathogénie aux perspectives cliniques

The aim of this article is a critical review of the main pathogenetic issues debated in Alzheimer disease, with a focus on the clinical perspectives that could derive from. The pertinence of the amyloid cascade hypothesis as a unique and causal explanation of cognitive deterioration is challenged in the light of recent therapeutic failures of clinical trials and increasing role of tau protein in clinical expression. The detection of very early and possibly preclinical stages of the disease emerges as a necessary condition for the efficacy of future amyloid or tau-oriented curative strategies. In this respect, the possibility of finding individual vulnerability markers--in the group of patients with "mild cognitive impairment" or even in cognitively intact subjects--represents a major challenge of the clinical research in this field

Proteomics in human Parkinson's disease research

During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been achieved, yet neither definite etiology nor unifying sequence of molecular events has been formally established. Current unmet needs in Parkinson's disease research include exploring new hypotheses regarding disease susceptibility, occurrence and progression, identifying reliable diagnostic, prognostic and therapeutic biomarkers, and translating basic research into appropriate disease-modifying strategies. The most popular view proposes that Parkinson's disease results from the complex interplay between genetic and environmental factors and mechanisms believed to be at work include oxidative stress, mitochondrial dysfunction, excitotoxicity, iron deposition and inflammation. More recently, a plethora of data has accumulated pinpointing an abnormal processing of the neuronal protein alpha-synuclein as a pivotal mechanism leading to aggregation, inclusions formation and degeneration. This protein-oriented scenario logically opens the door to the application of proteomic strategies to this field of research. We here review the current literature on proteomics applied to Parkinson's disease research, with particular emphasis on pathogenesis of sporadic Parkinson's disease in humans. We propose the view that Parkinson's disease may be an acquired or genetically-determined brain proteinopathy involving an abnormal processing of several, rather than individual neuronal proteins, and discuss some pre-analytical and analytical developments in proteomics that may help in verifying this concept

Amyloid deposition is decreasing in aging brains: an autopsy study of 1,599 older people

To explore cohort effects on age- and Alzheimer disease (AD)-related neuropathologic changes