Journal ArticleDOI
Alzheimer's Disease: Genes, Proteins, and Therapy
TLDR
Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.Abstract:
Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid β-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the β-amyloid precursor protein by the protease called γ-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought γ-...read more
Citations
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Journal ArticleDOI
Inflammation and therapeutic vaccination in CNS diseases.
TL;DR: Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches.
Journal ArticleDOI
Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases.
Erik N. T. P. Bakker,Brian J. Bacskai,Michal Arbel-Ornath,Roxana Aldea,Beatrice Bedussi,Alan Morris,Roy O. Weller,Roxana O. Carare,Roxana O. Carare +8 more
TL;DR: The role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain are reviewed and the different views on the possible routes for ISF drainage of thebrain are discussed in the context of pathological significance.
Journal ArticleDOI
Targeting soluble Aβ peptide with Tramiprosate for the treatment of brain amyloidosis
Francine Gervais,Julie Paquette,Céline Morissette,Pascale Krzywkowski,Mathilde Yu,Mounia Azzi,Diane Lacombe,Xianqi Kong,Ahmed Aman,Julie Laurin,Walter A. Szarek,Patrick Tremblay +11 more
TL;DR: It is proposed that Tramiprosate, which targets soluble Abeta, represents a new and promising therapeutic class of drugs for the treatment of AD.
Journal ArticleDOI
Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to beta-amyloid deposition in APP/PS1 double transgenic Alzheimer mice.
Tarja Malm,Milla Koistinaho,Maria Pärepalo,Tero Vatanen,Andreas Ooka,Stefan Karlsson,Jari Koistinaho +6 more
TL;DR: It is suggested that infiltration of BM-derived monocytic cells into the brain contributes to the development of microglial reaction in AD.
Journal ArticleDOI
Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease.
Christoph Schmitz,Christoph Schmitz,Christoph Schmitz,Bart P. F. Rutten,Bart P. F. Rutten,Bart P. F. Rutten,Andrea Pielen,Stephanie Schäfer,Stephanie Schäfer,Oliver Wirths,Oliver Wirths,Gunter Tremp,Christian Czech,Véronique Blanchard,Gerd Multhaup,Payam Rezaie,Hubert Korr,Hubert Korr,Harry W.M. Steinbusch,Harry W.M. Steinbusch,Laurent Pradier,Thomas A. Bayer,Thomas A. Bayer +22 more
TL;DR: Large loss of neurons was observed at sites of Abeta aggregation and surrounding astrocytes but, most importantly, was also clearly observed in areas of the parenchyma distant from plaques, pointing to the potential involvement of more than one mechanism in hippocampal neuron loss in this APP/PS-1 double-transgenic mouse model of Alzheimer's disease.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.
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