Search results for "ALZHEIMER'S DISEASE"
showing 10 items of 301 documents
Exploring the Virchow-Robin spaces function: A unified theory of brain diseases.
2016
Background: Cerebrospinal fluid (CSF) transport across the central nervous system (CNS) is no longer believed to be on the conventional lines. The Virchow-Robin space (VRS) that facilitates CSF transport from the basal cisterns into the brain interstitial fluid (ISF) has gained interest in a whole new array of studies. Moreover, new line of evidence suggests that VRS may be involved in different pathological mechanisms of brain diseases. Methods: Here, we review emerging studies proving the feasible role of VRS in sleep, Alzheimer's disease, chronic traumatic encephalopathy, and traumatic brain injury (TBI). Results: In this study, we have outlined the possible role of VRS in different path…
Anosognosia and Metacognition in Alzheimer's disease: Insights from Experimental Psychology
2015
International audience; While metacognition and anosognosia have long been studied as distinct concepts, more recently we have endeavored to construct a theoretical framework for exploring how metacognition can contribute to our understanding of anosognosia and vice versa. Following this approach, with a particular focus on Alzheimer's disease (AD), this chapter first gives an overview of the key experimental findings and issues on metacognition in AD patients: in particular, overconfidence and absolute awareness; the sensitivity approach; the fractionation of metacognition in AD; the neural substrates of metacognition in the Alzheimer brain; and metacognitive control in these patients. Sec…
Depressive Symptom Profiles Predict Specific Neurodegenerative Disease Syndromes in Early Stages
2020
Background: During early stages, patients with neurodegenerative diseases (NDG) often present with depressive symptoms. However, because depression is a heterogeneous disorder, more precise delineation of the specific depressive symptom profiles that arise early in distinct NDG syndromes is necessary to enhance patient diagnosis and care. Methods and Findings: Five-hundred and sixty four participants self-reported their depressive symptoms using the Geriatric Depression Scale (GDS), including 111 healthy older control subjects (NC) and 453 patients diagnosed with one of six NDGs who were at the mild stage of disease (CDR® Dementia Staging Instrument ≤ 1) [186 Alzheimer's disease (AD), 76 be…
HIGH PROPORTION OF DEMENTIA WITH LEWY BODIES IN THE POSTMORTEMS OF A MENTAL HOSPITAL IN GERMANY
1997
Objective. Dementia with Lewy bodies (DLB) is under-recognized in Germany. No data on the number of patients suffering from this condition in Germany are available at present. We were interested in the proportion of DLB in the postmortems of demented inpatients in the care of a psychogeriatric service. Design. In a retrospective study we examined consecutive postmortems of inpatients who died in one mental hospital. Setting. A suburban and rural old age psychiatry service in Germany. Patients. 103 consecutive postmortems had been performed from 9/1987 to 6/1995. Fifty-nine (57.3%) of all cases warranted the clinical diagnosis of dementia (DSM-III-R). Measures. The causes of dementia were ex…
A scientific approach to anti-ageing therapies: state of the art.
2008
A lasting dream of human beings is to reverse or at least postpone ageing. During the last years, an increasing number of scientific meetings, articles, and books have been devoted to anti-ageing therapies. This subject, full of misleading, simplistic, or wrong ideas, is very popular among the general public, whose imagery has been fascinated by all possible tools to delay ageing, getting immortality. Here, we discuss anti-ageing strategies aimed not to rejuvenate but to slow ageing and delay the onset of age-related diseases. These approaches should be able to substantially slow down the ageing process, extending our productive, youthful lives.
Selective Modulation of Aβ42 Production in Alzheimers Disease: Non-Steroidal Anti-Inflammatory Drugs and Beyond
2006
The amyloid-β (Aβ) peptides and in particular the longer, highly amyloidogenic isoform Aβ42 are believed by many to be the central disease-causing agents in Alzheimers disease (AD). Consequently, academic and pharmaceutical laboratories have focused on elucidating the mechanisms of Aβ production and developing strategies to diminish Aβ formation for treatment or prevention of AD. The most substantial advances have been made with respect to inhibitors of the γ-secretase enzyme, which catalyzes the final step in the generation of Aβ from the amyloid precursor protein (APP). Highly potent γ-secretase inhibitors which suppress production of all Aβ peptides are available today. However, due to t…
Imaging P-Glycoprotein Induction at the Blood–Brain Barrier of a β-Amyloidosis Mouse Model with 11C-Metoclopramide PET
2019
P-glycoprotein (ABC subfamily B member 1, ABCB1) plays an important role at the blood–brain barrier (BBB) in promoting clearance of neurotoxic β-amyloid (Aβ) peptides from the brain into the blood. ABCB1 expression and activity were found to be decreased in the brains of Alzheimer disease patients. Treatment with drugs that induce cerebral ABCB1 activity may be a promising approach to delay the build-up of Aβ deposits in the brain by enhancing clearance of Aβ peptides from the brain. The aim of this study was to investigate whether PET with the weak ABCB1 substrate radiotracer 11C-metoclopramide can measure ABCB1 induction at the BBB in a β-amyloidosis mouse model (APP/PS1-21 mice) and in w…
The unsolved relationship of brain aging and late-onset Alzheimer disease.
2009
Late-onset Alzheimer disease is the most common form of dementia and is strongly associated with age. Today, around 24 million people suffer from dementia and with aging of industrial populations this number will significantly increase throughout the next decades. An effective therapy that successfully decelerates or prevents the progressive neurodegeneration does not exist. Histopathologically Alzheimer disease is characterized by extensive extracellular amyloid beta (Abeta) plaques, intracellular neurofibrillary tangles (NFTs), synaptic loss and neuronal cell death in distinct brain regions. The molecular correlation of Abeta or NFTs and development of late-onset Alzheimer disease needs f…
Thioflavin T templates amyloid β(1–40) conformation and aggregation pathway
2015
Aβ(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies to control the occurring events. To this purpose the exploitation of small molecules interacting with Aβ aggregation represents one of the possible routes. Moreover, the use specific labeling has represented so far one of the most common and effective methods to investigate such a process. This possibility in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effe…
The Metalloprotease Meprin β Generates Amino Terminal-truncated Amyloid β Peptide Species
2012
The amyloid β (Aβ) peptide, which is abundantly found in the brains of patients suffering from Alzheimer disease, is central in the pathogenesis of this disease. Therefore, to understand the processing of the amyloid precursor protein (APP) is of critical importance. Recently, we demonstrated that the metalloprotease meprin β cleaves APP and liberates soluble N-terminal APP (N-APP) fragments. In this work, we present evidence that meprin β can also process APP in a manner reminiscent of β-secretase. We identified cleavage sites of meprin β in the amyloid β sequence of the wild type and Swedish mutant of APP at positions p1 and p2, thereby generating Aβ variants starting at the first or seco…