Objective: Frontotemporal dementia (FTD) is a neurodegenerative disease that erodes uniquely human aspects of social behavior and emotion. The illness features a characteristic pattern of early injury to anterior cingulate and frontoinsular cortex. These regions, though often considered ancient in phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large bipolar projection neuron found only in great apes and humans. Despite progress toward understanding the genetic and molecular bases of FTD, no class of selectively vulnerable neurons has been identified. Methods: Using unbiased stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons in FTD (n ϭ 7), Alzheimer's disease (n ϭ 5), and age-matched nonneurological control subjects (n ϭ 7). Neuronal morphology and immunohistochemical staining patterns provided further information about VEN susceptibility. Results: FTD was associated with early, severe, and selective VEN losses, including a 74% reduction in VENs per section compared with control subjects. VEN dropout was not attributable to general neuronal loss and was seen across FTD pathological subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In contrast, patients with Alzheimer's disease showed normal VEN counts and morphology despite extensive local neurofibrillary pathology. Interpretation: VEN loss links FTD to its signature regional pattern. The findings suggest a new framework for understanding how evolution may have rendered the human brain vulnerable to specific forms of degenerative illness.Ann Neurol 2006;60:660 -667 Primate brain evolution has led to increasing frontal encephalization, hemispheric functional lateralization, and maturational delay. At the level of neuronal morphology, however, little differentiates humans from even our distant mammalian ancestors. Von Economo neurons (VENs) provide a notable exception. These large bipolar projection neurons are a unique feature of great apes and humans.

In prion-infected mice, both the Notch-1 intracellular domain transcription factor (NICD) and the disease-causing prion protein (PrP Sc ) increase in the brain preceding dendritic atrophy and loss. Because the drug LY411575 inhibits the ␥-secretase-catalyzed cleavage of Notch-1 that produces NICD, we asked whether this ␥-secretase inhibitor (GSI) might prevent dendritic degeneration in mice with scrapie. At 50 d postinoculation with Rocky Mountain Laboratory (RML) prions, mice were given GSI orally for 43-60 d. Because we did not expect GSI to produce a reduction of PrP Sc levels in brain, we added quinacrine (Qa) to the treatment regimen. Qa inhibits PrP Sc formation in cultured cells. The combination of GSI and Qa reduced PrP Sc by Ϸ95% in the neocortex and hippocampus but only Ϸ50% in the thalamus at the site of prion inoculation. The GSI plus Qa combination prevented dendritic atrophy and loss, but GSI alone did not. Even though GSI reduced NICD levels to a greater extent than GSI plus Qa, it was unable to prevent dendritic degeneration. Whether a balance between NICD and dendrite growth-stimulating factors was achieved with GSI plus Qa but not GSI alone remains to be determined. Although the combination of GSI and Qa diminished PrP Sc in the brains of RML-infected mice, GSI toxicity prevented us from being able to assess the effect the GSI plus Qa combination on incubation times. Whether less toxic GSIs can be used in place of LY411575 to prolong survival remains to be determined.Creutzfeldt-Jakob disease ͉ neuropathology ͉ prion disease ͉ therapy ͉ scrapie

De-institutionalization of mental health patients has evolved, over nearly 3 generations now, to a status quo of mental health patients experiencing myriad contacts with first-responders, primarily police, in lieu of care. The current institutions in which these patients rotate through are psychiatric emergency units, emergency rooms, jails, and prisons. Although more police are now specially trained to respond to calls that involve mental health patients, the criminalization of persons with mental illness has been steadily increasing over the past several decades. There have also been deaths. The Crisis Intervention Team (CIT) model fosters mental health acumen among first responders, and facilitates collaboration among first responders, mental health professionals, and mental health patients and their families. Here, we review some modern, large city configurations of CIT, the co-responder model, the mitigating effects of critically situated community-based programs, as well as barriers to the success of joint efforts to better address this pressing problem.