Journal of Neuropathology & Experimental Neurology:
In This Issue
The authors review several β-amyloid-degrading enzymes, speculate on their possible therapeutic benefits in the treatment of Alzheimer disease, and summarize potential delivery methods.
see page 944
Stages of the Pathologic Process in Alzheimer Disease From 1 to 100 Years
Braak et al examined Alzheimer-related pathology in 2332 brains from individuals 1 to 100 years old. Their data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem (particularly locus coeruleus) rather than in the transentorhinal region. Tau-positive brainstem lesions developed before cortical amyloid deposition.
see page 960
α-Internexin in Oligodendrogliomas
The loss of 1p/19q has become a valuable molecular diagnostic test to delineate oligodendrogliomas. Eigenbrod et al test the use of using α-internexin as a surrogate marker for 1p/19q deletion and find that it represents a valuable adjunct test.
see page 970
Angiogenesis Challenged in Brain Metastases
The growth of brain metastases is generally assumed to be essential for angiogenesis. Bugyik et al provide data suggesting that sprouting angiogenesis is not needed for the incipient growth of cerebral metastases.
see page 979
B-Cell Depletion Benefits Marmoset EAE
Monoclonal antibody (mAb)-induced B-cell depletion benefits multiple sclerosis patients. Kap et al assessed effects of an anti-CD20 mAb B-cell depletion on CNS pathology in marmoset EAE. In vivo and postmortem neuroimaging revealed gray and white matter lesions that were reduced or absent in treated animals. Histologic analysis confirmed that inflammation, demyelination, and axonal damage were substantially reduced in the CNS and optic nerves of mAb-treated marmosets. These data underline the central pathogenetic roles of B-cells in CNS inflammatory-demyelinating disease.
see page 992
Truncation of tau at E391 Promotes Early Pathologic Changes in Transgenic Mice
McMillan et al used a mouse model to show that truncated but otherwise wild-type human tau is sufficient to drive pretangle pathologic changes, including accumulation of insoluble tau, somatodendritic redistribution, formation of pathologic conformations, and dual phosphorylation of tau. These results suggest that changes in tau proteolysis can initiate tauopathy.
see page 1006
NOX2 in Glutamate Neurotoxicity
Guemez-Gamboa et al profiled glutamate receptor subtypes involved in NADPH oxidase (NOX2) activation and neuronal death after intrastriatal glutamate injections in mice. NOX2-deficient mice were less vulnerable to excitotoxicity and had reduced reactive oxygen species production, protein nitrosylation, microglial reactivity, and calpain activation than wild-type mice. The results suggest that NOX2 is stimulated by glutamate in neurons and microglia via activation of ionotropic and metabotropic receptors. Neuronal damage involves ROS production by NOX2, which in turn contributes to calpain activation.
see page 1020
Mouse vs. Human tau
Using a tau knockout model, the authors show that tau does not contribute to the pathogenesis of mouse prion disease. This is in contrast to Alzheimer and frontal temporal lobar degenerations, in which prion-induced phosphorylation of tau results in neuronal degeneration.
see page 1036
Experimental Blast Injury to the Gyrencephalic Brain
de Lanerolle et al determined the effects of blast injury induced in military combat-relevant scenarios on the brains of swine. Blasts induced minimal overt damage, but there were astrocyte activation and proliferation and periventricular axonal injury. They suggest that these subtle alterations may have long-term consequences; similar alterations may be related to cognitive and mood disorders after blast injury in humans.
see page 1046