Novel Targets for Alzheimer's Disease Treatment: Medin and PLD3 Blog post by Nina Culum, MSc Alzheimers disease, the most common type of dementia worldwide, is becoming an increasingly serious global health problem [1, 2]. Owing largely to aging populations and increased life expectancy, the number of individuals living with dementia has more than doubled over the past three decades, imposing significant economic and disease burdens on both families and societies [2]. Despite this increased prevalence, a cure for Alzheimers disease remains elusive. Extraneuronal amyloid plaques and intraneuronal neurofibrillary tangles composed of amyloid-_ (A_) and hyperphosphorylated tau proteins, respectively, are thought to underlie neuronal damage in Alzheimers disease [3]. However, recent neuropathological studies have indicated that the disease is more heterogeneous than originally presumed. For example, _-synuclein and microvascular disease have now been implicated in the neuropathology of late-onset Alzheimers disease [3]. Therefore, progress in effective drug development is more likely to occur if more than one pathway is considered [4]. Two recent Nature publications have potentially identified new therapeutic targets for Alzheimers disease, including medin [5] and phospholipase D3 (PLD3) [6], which we summarize in this mini-review. https://insidescientific.com/wp-content/uploads/2022/09/Strategic-Approaches-to-Age-Related-Metabolic-Insufficiency-and-Transition-into-Dementia-Syndrome_FI.jpg Strategic Approaches to Age-Related Metabolic Insufficiency and Transition into Dementia Syndrome In this webinar, Dennis Turner, MA, MD, delves into dementia syndrome, the metabolic changes that occur, and the importance of proper physiological monitoring of animal models. WATCH NOW

The role of medin in Alzheimer's disease

Study motivation: Medin, the most common human amyloid known to date, has been found to form vascular aggregates in aging wildtype mice, causing cerebrovascular dysfunction. Aggregates of medin have also been found postmortem in cerebral arterioles of patients with vascular dementia. Therefore, Wagner et al. sought to study the role of medin in mouse models of cerebral _-amyloidosis and postmortem human brain tissue to determine whether its increased levels are a cause or consequence of Alzheimers disease [5]. Key findings: In two transgenic A_ precursor protein (APP) mouse models, staining with the MFG-E8 antibody, which has been shown to recognize extracellular medin aggregates in the vasculature of aging wildtype mice, revealed that medin extensively co-localizes with amyloid plaques ( Figure 1 ). Additionally, medin deficiency was found to reduce cerebral A_ angiopathy (CAA) as well as vascular A_ deposition. Although the authors could not biochemically confirm the presence of medin in the mouse samples, these data demonstrate that the medin precursor protein MFG-E8 is highly enriched in the vasculature and increases further with CAA. [fusion_builder_column type="1_1" layout="1_1" align_self="auto" content_layout="column" align_content="flex-start" valign_content="flex-start" content_wrap="wrap" spacing="" center_content="no" column_tag="div" link="" target="_self" link_description="" min_height="" hide_on_mobile="small-visibility,medium-visibility,large-visibility" sticky_display="normal,sticky" class="" id="" background_image_id="" type_medium="" type_small="" order_medium="0" order_small="0" spacing_left_medium="" spacing_right_medium="" spacing_left_small="" spacing_right_small="" spacing_left="" spacing_right="" margin_top_medium="" margin_bottom_medium="" margin_top_small="" margin_bottom_small="" margin_top="30px" margin_bottom="30px" padding_top_medium="" padding_right_medium="" padding_bottom_medium="" padding_left_medium="" padding_top_small="" padding_right_small="" padding_bottom_small="" padding_left_small="" padding_top="20px" padding_right="20px" padding_bottom="20px" padding_left="20px" hover_type="none" border_sizes_top="" border_sizes_right="" border_sizes_bottom="" border_sizes_left="" border_color="" hue="" saturation="" lightness="" alpha="" border_style="solid" border_radius_top_left="" border_radius_top_right="" border_radius_bottom_right="" border_radius_bottom_left="" box_shadow="no" box_shadow_vertical="" box_shadow_horizontal="" box_shadow_blur="0" box_shadow_spread="0" box_shadow_color="" box_shadow_style="" z_index_subgroup="regular" z_index="" z_index_hover="" overflow="" background_type="single" gradient_start_color="" gradient_end_color="" gradient_start_position="0" gradient_end_position="100" gradient_type="linear" radial_direction="center center" linear_angle="180" background_color="#f5f5f5" background_image="" lazy_load="avada" skip_lazy_load="" background_position="left top" background_repeat="no-repeat" background_blend_mode="none" render_logics="" sticky="off" sticky_devices="small-visibility,medium-visibility,large-visibility" sticky_offset="" filter_type="regular" filter_hue="0" filter_saturation="100" filter_brightness="100" filter_contrast="100" filter_invert="0" filter_sepia="0" filter_opacity="100"