PAPER Berk C, Sabbagh MN

Successes and failures for drugs in late-stage development for Alzheimer's disease.

Drugs Aging. 2013 Oct;30(10):783-92. PubMed: 23943247

PAPER Rongve A, Vossius C, Nore S, Testad I, Aarsland D

Time until nursing home admission in people with mild dementia: comparison of dementia with Lewy bodies and Alzheimer's dementia.

Int J Geriatr Psychiatry. 2013 Aug 13; PubMed: 23943275

PAPER Sontag JM, Nunbhakdi-Craig V, Sontag E

Leucine carboxyl methyltransferase 1 (LCMT1)-dependent Methylation Regulates the Association of Protein Phosphatase 2A and Tau with Plasma Membrane Microdomains in Neuroblastoma Cells.

J Biol Chem. 2013 Sep 20;288(38):27396-405. PubMed: 23943618

PAPER Zotova E, Bharambe V, Cheaveau M, Morgan W, Holmes C, Harris S, Neal JW, Love S, Nicoll JA, Boche D

Inflammatory components in human Alzheimer's disease and after active amyloid-β42 immunization.

Brain. 2013 Sep;136(Pt 9):2677-96. PubMed: 23943781

Mark Cookson on The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy.

COMMENT The key thing these authors show in this paper, and this is why it is an important study, is that Fbxo7 mutations interact with an established pathway for recessive parkinsonism. The authors clearly show that the mutations are loss of function, which is p

PAPER Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, Abramov AY, Hardy J, Wood NW, Whitworth AJ, Laman H, Plun-Favreau H

The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy.

Nat Neurosci. 2013 Sep;16(9):1257-65. PubMed: 23933751

Benjamin Wolozin on Suppression of eIF2α kinases alleviates Alzheimer's disease-related plasticity and memory deficits.

COMMENT The paper by the Klann group presents an elegant study that highlights the importance of translational control at the synapse in the pathophysiology of Amyloidβ, and perhaps, neurodegeneration generally. When Aβ causes synaptic toxicity, it necessarily ca

PAPER Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P

Pharmacological brake-release of mRNA translation enhances cognitive memory.

Elife. 2013;2:e00498. PubMed: 23741617

PAPER Trinh MA, Kaphzan H, Wek RC, Pierre P, Cavener DR, Klann E

Brain-specific disruption of the eIF2α kinase PERK decreases ATF4 expression and impairs behavioral flexibility.

Cell Rep. 2012 Jun 28;1(6):676-88. PubMed: 22813743

PAPER Klann E, Dever TE

Biochemical mechanisms for translational regulation in synaptic plasticity.

Nat Rev Neurosci. 2004 Dec;5(12):931-42. PubMed: 15550948

Gunnar Gouras on Activity-Induced Convergence of APP and BACE-1 in Acidic Microdomains via an Endocytosis-Dependent Pathway.

COMMENT This is a very nice study using high-level microscopy to provide evidence for BACE1 and APP converging in dendritic endosomes of cultured neurons by live cell imaging following synaptic activation. It is less clear what this work means for Alzheimer’s dis

Yasuyuki Mitani on Alzheimer's disease mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD production.

COMMENT The finding of a decrease in the AICD 49-99/50-99 ratio due to APP mutations near the γ- or ε-site is intriguing, and may partly answer why these mutations increase the Aβ 42/40 ratio if the step-wise cleavage hypothesis is correct. That GSMs have no effe

Yasuyuki Mitani

United States

Steve Barger on Curbing Innate Immunity Boosts Synapses, Cognition

COMMENT This is a fascinating report that seems to help clarify the roles of inflammation-related immune agents in AD. There has been some confusion and controversy arising from the findings that innate immune reactions appear to contribute to the development of

Jason Shepherd on Neural Activity Tips Endosomal Balance, Hastens Amyloid Pathology

COMMENT The study by Das et al. was meticulously conducted and provides an important platform for further work in understanding how Aβ production normally occurs. It has been known for some time that Aβ secretion is activity-dependent, but the precise mechanisms