Amyloid-β (Aβ) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer's disease.

Background: Anti-amyloid-β (Aβ) immunotherapy trials have revealed amyloid-related imaging abnormalities (ARIA) as the most prevalent and serious adverse events linked to pathological changes in cerebral vasculature. Recent studies underscore the critical involvement of perivascular macrophages and the infiltration of peripheral immune cells in regulating cerebrovascular damage. Specifically, Aβ antibodies engaged at cerebral amyloid angiopathy (CAA) deposits trigger perivascular macrophage activation and the upregulation of genes associated with vascular permeability.

Amyloid-β (Aβ) immunotherapy induced microhemorrhages are associated with activated perivascular macrophages and peripheral monocyte recruitment in Alzheimer's disease mice.

Background: Amyloid-related imaging abnormalities (ARIA) have been identified as the most common and serious adverse events resulting from pathological changes in the cerebral vasculature during several recent anti-amyloid-β (Aβ) immunotherapy trials. However, the precise cellular and molecular mechanisms underlying how amyloid immunotherapy enhances cerebral amyloid angiopathy (CAA)-mediated alterations in vascular permeability and microhemorrhages are not currently understood. Interestingly, brain perivascular macrophages have been implicated in regulating CAA deposition and cerebrovascular function however, further investigations are required to understand how perivascular macrophages play a role in enhancing CAA-related vascular permeability and microhemorrhages associated with amyloid immunotherapy.

Metabotropic Glutamate Receptors Modulate Exocytotic Tau Release and Propagation.

Using synaptosomes purified from the brains of two transgenic mouse models overexpressing mutated human tau (TgP301S and Tg4510) and brains of patients with sporadic Alzheimer's disease, we showed that aggregated and hyperphosphorylated tau was both present in purified synaptosomes and released in a calcium- and synaptosome-associated protein of 25 kDa (SNAP25)-dependent manner. In all mouse and human synaptosomal preparations, tau release was inhibited by the selective metabotropic glutamate receptor 2/3 (mGluR2/3) agonist LY379268, an effect prevented by the selective mGlu2/3 antagonist LY341495. LY379268 was also able to block pathologic tau propagation between primary neurons in an in vitro microfluidic cellular model.

Decreased sensitivity of NMDA receptors on dopaminergic neurons from the posterior ventral tegmental area following chronic nondependent alcohol consumption.

Background: The mesocorticolimbic dopamine system mediates the reinforcing effects of salient stimuli, including drugs of abuse. Nondependent chronic alcohol consumption modifies this system, resulting in an increased number of spontaneously active dopamine neurons in the posterior ventral tegmental area (VTA) of alcohol-preferring (P) rats. Enhanced responses of postsynaptic glutamate receptors may contribute to the increase in active dopamine neurons.

Combined effect of depressive symptoms and hostility on autonomic nervous system function.

Depression and hostility have been separately related to indicators of sympathetic hyperactivation and parasympathetic hypoactivation. We examined the associations of depressive symptoms, hostility, and their interaction with pre-ejection period (PEP) and high frequency heart rate variability (HRV), specific indices of sympathetic and parasympathetic cardiac control, respectively. Healthy, young adults (N=120) completed questionnaires assessing depressive symptoms and hostility and underwent autonomic testing.

Hostility now, depression later? Longitudinal associations among emotional risk factors for coronary artery disease.

Background/purpose: Given that emotional risk factors for coronary artery disease (CAD) tend to cluster within individuals, surprisingly little is known about how these negative emotions might influence one another over time. We examined the longitudinal associations among measures of depressive symptoms and hostility/anger in a cohort of 296 healthy, older adults.

Methods: Participants completed the Beck Depression Inventory-II (BDI-II), Cook-Medley Hostility (Ho) scale, and Anger-In and Anger-Out subscales of the State-Trait Anger Expression Inventory at baseline and 6-year follow-up.