edaravone on ALS2006/12/08 15:16:36

Yoshino H, Kimura A : Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis( Phase II study ). Amyotrophic Lateral Sclerosis 2006;7:241-245 ラジカットがALSに有効であるという論文が初めて、のったようです。はやく保険適応となることを祈ります。 この論文について考察しているブログをみつけました。じつによく勉強しています。 http://blog.goo.ne.jp/pkcdelta/e/eaf16d6cdb47efd7fdbd3ba636ddae83

Alzheimer2006/11/19 19:29:41

Reviews A Century of Alzheimer's Disease Michel Goedert and Maria Grazia Spillantini Science 3 November 2006: 777-781. 100 Years and Counting: Prospects for Defeating Alzheimer's Disease Erik D. Roberson and Lennart Mucke Science 3 November 2006: 781-784. またしてもAlzheimerのreview.これ読んでると今年終わりそう。この人がAlzheimerです。 Scienceの引用でDarwinのsiteは巨大だ。 darwin-online.org.uk/

ALSの花見、紅葉狩り2006/10/25 19:09:05

吉野英:ALS患者のお花見と紅葉狩り--やすらぎのある難病病棟をめざして. 医学のあゆみ 219:156-157,2006

わたしのアイデアも少し入っているので紹介しておきます。これをみて、見学希望の方もあらわれたとか。

Alzheimer2006/08/02 22:16:26

The Lancet 2006; 368:387-403

DOI:10.1016/S0140-6736(06)69113-7

Alzheimer's disease

Dr Kaj Blennow MD

nature Medicineがおわらないうちの膨大のreviewがまた発表された。今週中に処理します。

Summary Alzheimer's disease is the most common cause of dementia. Research advances have enabled detailed understanding of the molecular pathogenesis of the hallmarks of the disease—ie, plaques, composed of amyloid β (Aβ), and tangles, composed of hyperphosphorylated tau. However, as our knowledge increases so does our appreciation for the pathogenic complexity of the disorder. Familial Alzheimer's disease is a very rare autosomal dominant disease with early onset, caused by mutations in the amyloid precursor protein and presenilin genes, both linked to Aβ metabolism. By contrast with familial disease, sporadic Alzheimer's disease is very common with more than 15 million people affected worldwide. The cause of the sporadic form of the disease is unknown, probably because the disease is heterogeneous, caused by ageing in concert with a complex interaction of both genetic and environmental risk factors. This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies.

Aβ star: a light onto synaptic dysfunction?2006/07/24 07:20:30

Nature Medicine 12, 760 - 761 (2006) doi:10.1038/nm0706-760

Learning and memory is impaired in a mouse model of Alzheimer disease. An Aβ12-mer called Aβ* may be responsible for these cognitive deficits.

The ups and downs of Abeta2006/07/23 08:00:16

Nature Medicine 12, 758 - 759 (2006) doi:10.1038/nm0706-758 Dennis J Selkoe

How do A levels increase in individuals with Alzheimer disease? Recent work suggests that some forms of neuronal activity can drive Abeta accumulation in the brain.

Neuronal release of the peptide is physiologically regulated by synaptic activity throughout life.(Cirrito, J.R. et al. Neuron 48, 913–922 (2005))

Physiological (and pharmacological) changes in neuronal activity, especially synaptic activity, may continuously alter the levels of both A40 and the far more amyloidogenic A42 species in brain regions prone to formation of amyloid plaques.

Aβの生理的役割にするneuronの図がでています。

Amyloid at the blood vessel wall2006/07/20 07:34:40

Nature Medicine 12, 756 - 757 (2006) doi:10.1038/nm0706-756

An APP gene duplication found in French families with beta-amyloidopathy suggests a link between dementia and the vasculature.

AlzheimerとAmyloid angiopathy(AA)はきってもきれない関係にあり、昔Alzheimerの100%がAAだと書いてあったが、最近学習した時には70%になっていた。遺伝性のAAがあることがよく知られている。

Nature Genetics 38, 24 - 26 (2006) Published online: 20 December 2005; | doi:10.1038/ng1718

APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy Anne Rovelet-Lecrux et al.

We report duplication of the APP locus on chromosome 21 in five families with autosomal dominant early-onset Alzheimer disease (ADEOAD) and cerebral amyloid angiopathy (CAA). Among these families, the duplicated segments had a minimal size ranging from 0.58 to 6.37 Mb. Brains from individuals with APP duplication showed abundant parenchymal and vascular deposits of amyloid-beta peptides. Duplication of the APP locus, resulting in accumulation of amyloid-beta peptides, causes ADEOAD with CAA.

このAPP duplicationsの人の表現型はさまざまで、痴呆、出血、その両者の場合がある。APPの変異で発生する(Flemish mutation)と似ている。あるいはDutch Type AAとも。

Genetic variability in the expression of these loci contribute to the risk of 'sporadic' disease.つまり我々のよく知るAAにもこういったのが関与する。Singleton, A. , Myers, A. & Hardy, J. Hum. Mol. Genet. 13, R123–R126 (2004) Down(trisomy 21)の人は脳出血しない。 amylopidopathy における血管と実質病変のoverlapについては再考を要する。 Abeta vaccination(AN1792)のmeningoencephalitisには抗体によるmicrovascular damageが関与。

Alzheimerもmicrohemorrhageで、症状の進展にもvascular lesionが関与しているものと考えられる。

APP is involved in blood clotting.(PNAS 102.18135-18140,2005 Abetaにはdamage-response roleがある。出血したときの血管のvascular sealant。neuronal depressant。生理作用もあるらしい。

Can the immune system fight Alzheimer disease?2006/07/18 21:18:19

Nature Medicine 12, 755 - 756 (2006) doi:10.1038/nm0706-755

Mobilizing the immune system may be a promising strategy to fight Alzheimer disease. A clinical trial has shed light on the therapeutic potential—and the pitfalls—of Aß immunization.

Schenk, D. et al. Nature 400, 173–177 (1999) the startling discovery that immunizing transgenic mice that overexpressed human amyloid with the human Abeta42 peptide(AN-1792) prevented the expected buildup of amyloid plaques in the brain

Clinical trial Gilman, S. et al. Neurology 64, 1553–1562 (2005) Fox, N.C. et al. Neurology 64, 1563–1572 (2005)

An unexpected serious adverse event when 6% of the treated individuals developed meningoencephalitis

Pinpointing plaques with PIB2006/07/17 17:50:28

Nature Medicine 12, 753 - 754 (2006) doi:10.1038/nm0706-753

The promise of disease-modifying treatments for Alzheimer disease calls for biomarkers that enable early diagnosis. A new discovery shows how to visualize amyloid pathology in living Alzheimer patients.

In a recent paper(Klunk, W.E. et al. Ann. Neurol. 55, 306–319 (2004). ), Klunk and coworkers introduced amyloid imaging as a new principle, enabling direct visualization of amyloid plaques in the living human brain. Using a novel positron emission tomography (PET) tracer called Pittsburgh Compound-B (PIB), the authors found marked retention of the molecule in Alzheimer disease patients in areas of the brain known to contain large amounts of A plaques.

Alzheimer disease2006/07/17 16:06:31

Nature Medicine 2006年6月 Focus の特集。onlineでfreeでみれます。しばらくこれを抄読します。

Introduction

From imaging to immunotherapy, and synapses to -secretase: these are among the most exciting findings in the field of Alzheimer disease from the past three years, according to leading scientists. Many hope that these discoveries will soon lead to a cure for this devastating illness, which affects approximately 4.5 million individuals in the US alone. In countries such as Japan, where the proportion of aged individuals is expected to almost double over the next 50 years, tackling Alzheimer disease is crucial for safeguarding the health of the population...........

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