Freaking Out in a Moonage Daydream

Artist: Eleanor Lutz

Got books on the brain? Why not get some books on the brain? (Work it out.)

The 2014 Society for Neuroscience Annual Meeting is taking place November 15-19 in Washington D.C. If you’re attending the meeting, stop by booth 200 to check out these books and more.

Concussion Care Manual: A Practical Guide by David L Brody

Rhythms of the Brain by Gyorgy Buzsaki

The Aesthetic Brain: How We Evolved to Desire Beauty and Enjoy Art by Anjan Chatterjee

The OMICs: Applications in Neuroscience edited by Giovanni Coppola

Cajal’s Butterflies of the Soul: Science and Art by Javier DeFelipe

Ignorance: How It Drives Science by Stuart Firestein

Consciousness and the Social Brain by Michael S. A. Graziano

Introduction to Neuropsychopharmacology by Leslie Iversen, Susan D. Iversen, Floyd E. Bloom, and Robert H. Roth

Plants and the Human Brainby David O. Kennedy

Neuroglia, 3rd Edition edited by Helmut Kettenmann and Bruce R. Ransom

Integrated Neuroscience and Neurology: A Clinical Case History Problem Solving Approach, 2nd Editionby Elliott M. Marcus, Stanley Jacobson, and Thomas Sabin

Drugged: The Science and Culture Behind Psychotropic Drugs by Richard J. Miller

The Oxford Handbook of Attention edited by Kia Nobre and Sabine Kastner

The First Brain: The Neuroscience of Planarians by Oné R. Pagán

The Altruistic Brain: How We Are Naturally Good by Donald W. Pfaff

Angelo Mosso’s Circulation of Blood in the Human Brain edited with commentary by Marcus E. Raichle and Gordon M. Shepherd

Brain Architecture: Understanding the Basic Plan, Second Edition by Larry W. Swanson

Neuroanatomical Terminology: A Lexicon of Classical Origins and Historical Foundations by Larry Swanson

The Brain Supremacy: Notes from the frontiers of neuroscience by Kathleen Taylor          

Why Humans Like to Cry: Tragedy, Evolution, and the Brain by Michael Trimble

Your Brain on Food: How Chemicals Control Your Thoughts and Feelings, 2nd Edition by Gary L. Wenk

Flicker: Your Brain on Movies by Jeffrey M. Zacks

Novel culture system replicates course of Alzheimer’s disease, confirms amyloid hypothesis

An innovative laboratory culture system has succeeded, for the first time, in reproducing the full course of events underlying the development of Alzheimer’s disease. Using the system they developed, investigators from the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH) now provide the first clear evidence supporting the hypothesis that deposition of beta-amyloid plaques in the brain is the first step in a cascade leading to the devastating neurodegenerative disease. They also identify the essential role in that process of an enzyme, inhibition of which could be a therapeutic target.

"Originally put forth in the mid-1980s, the amyloid hypothesis maintained that beta-amyloid deposits in the brain set off all subsequent events – the neurofibrillary tangles that choke the insides of neurons, neuronal cell death, and inflammation leading to a vicious cycle of massive cell death," says Rudolph Tanzi, PhD, director of the MGH Genetics and Aging Research Unit and co-senior author of the report receiving advance online publication in Nature. “One of the biggest questions since then has been whether beta-amyloid actually triggers the formation of the tangles that kill neurons. In this new system that we call ‘Alzheimer’s-in-a-dish,’ we’ve been able to show for the first time that amyloid deposition is sufficient to lead to tangles and subsequent cell death.”

While the mouse models of Alzheimer’s disease that express the gene variants causing the inherited early-onset form of the disease do develop amyloid plaques in their brains and memory deficits, the neurofibrillary tangles that cause most of the damage do not appear. Other models succeed in producing tangles but not plaques. Cultured neurons from human patients with Alzheimer’s exhibit elevated levels of the toxic form of amyloid found in plaques and the abnormal version of the tau protein that makes up tangles, but not actual plaques and tangles.

Genetics and Aging Research Unit investigator Doo Yeon Kim, PhD, co-senior author of the Nature paper, realized that the liquid two-dimensional systems usually used to grow cultured cells poorly represent the gelatinous three-dimensional environment within the brain. Instead the MGH team used a gel-based, three-dimensional culture system to grow human neural stem cells that carried variants in two genes – the amyloid precursor protein and presenilin 1 – known to underlie early-onset familial Alzheimer’s Disease (FAD). Both of those genes were co-discovered in Tanzi’s laboratory.

After growing for six weeks, the FAD-variant cells were found to have significant increases in both the typical form of beta-amyloid and the toxic form associated with Alzheimer’s. The variant cells also contained the neurofibrillary tangles that choke the inside of nerve cells causing cell death. Blocking steps known to be essential for the formation of amyloid plaques also prevented the formation of the tangles, confirming amyloid’s role in initiating the process. The version of tau found in tangles is characterized by the presence of excess phosphate molecules, and when the team investigated possible ways of blocking tau production, they found that inhibiting the action of an enzyme called GSK3-beta – known to phosphorylate tau in human neurons – prevented the formation of tau aggregates and tangles even in the presence of abundant beta-amyloid and amyloid plaques