APP x LRP1

Last update 08 May 2025

Basic Info

Related Targets

APPLRP1

Drugs associated with APP x LRP1

MT007-LRPIV

Target

APP x LRP1

Mechanism

APP inhibitors [+1]

Active Org.-

Originator Org.

Socratech LLC

Active Indication-

Inactive Indication

Alzheimer Disease

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with APP x LRP1

100 Translational Medicine associated with APP x LRP1

0 Patents (Medical) associated with APP x LRP1

316

Literatures (Medical) associated with APP x LRP1

01 Aug 2025·Brain, Behavior, and Immunity

Sex-specific effects of chronic alcohol consumption across the lifespan in the transgenic Alzheimer’s Disease (TgF344-AD) rat model

Article

Author: Lutzke, Ashley ; Vore, Andrew S ; Savage, Lisa M ; Fischer, Abigail ; Gano, Anny ; Trapp, Sarah ; Deak, Terrence ; Marsland, Paige

Alcohol consumption across the lifespan contributes to mood fluctuations and cognitive dysfunction, two neurobehavioral features also associated with Alzheimer's Disease and Related Dementias (ADRD). Yet, few studies have used rodent models to determine how a history of ethanol consumption across the lifespan might contribute to neurobehavioral and neuropathological features of ADRD. We exposed Wild Type (WT) and transgenic Fischer 344 CE rats (TgF344-AD) that have been genetically modified to express the human Amyloid Precursor Protein (APP) and presenilin-1 genes with mutations, to ethanol using a chronic, intermittent ethanol consumption model. Beginning at P28, rats were given a single bottle 10 % ethanol solution for 2 consecutive days, followed by 2 days of tap water. This pattern (2 days on, days off) was repeated for a total of 12 cycles until rats reached the age of ∼ 3 months, and repeated at 6 (Exp 1 and Exp 2) and 9 months of age (Exp 2). In experiment 1, ethanol consumption decreased alternations in a spontaneous alternation task in females, only at the 3-month time point, whereas TgF344-AD females showed increased contextual fear conditioning in the test of retention and reinstatement tests at 6 months of age. In experiment 2, a battery of anxiety-like behaviors (Elevated Plus Maze, Marble Burying, and Novelty Induced Hypophagia) were assessed following a 2-week abstinence period at 3, 6, and 9 months of age in ethanol-consuming rats. Data from the EPM and marble burying tasks revealed evidence of heightened anxiety-like behavior in Tg-F344-AD rats that varied by sex and age, with no significant effects of ethanol. In the novelty-induced hypophagia task, males with a history of ethanol consumption had a lower latency to approach a familiar, salient reward at 3 months old, but effects of ethanol were overall minimal. Examination of dorsal hippocampal gene expression at 6 months of age under basal conditions also revealed predominantly genotype and sex-specific effects on inflammation- and AD-related genes (App, Il-6, Bace1, Rage, Lrp-1). When examined at 9 months old following LPS challenge, ethanol increased inflammatory genes in males (Il-1β, Il-6) in the hippocampus, whereas ethanol decreased several inflammatory and AD-related genes (Hmgb1, Rage, Bace1, Lrp-1) in TgF344-AD females. Overall, these data provide further evidence that females are especially vulnerable to AD, and that a history of ethanol consumption had selective, rather than global, effects on AD- and inflammation-related genes following an inflammatory stimulus.

01 Jun 2025·IBRO Neuroscience Reports

Lipidopathy disrupts peripheral and central amyloid clearance in Alzheimer's disease: Where are our knowledge

Review

Author: Moradi, Fatemeh ; Gorgich, Enam Alhagh Charkhat ; Darabi, Shahram ; Rustamzadeh, Auob

Amyloid-beta (Aβ) production is a normal physiological process, essential for neuronal function. However, an imbalance in Aβ production and clearance is the central pathological feature of Alzheimer's disease (AD), leading to the accumulation of Aβ plaques in the brain. Low-density lipoprotein receptor-related protein 1 (LRP1) plays a critical role in both the central clearance of Aβ from the brain and its peripheral transport to visceral organs. Disruptions in these processes contribute to the accumulation of Aβ in the central nervous system (CNS) and the progression of AD. Recent research emphasizes the need for a broader focus on the systemic effects of organs outside the brain, particularly in the context of AD prevention and treatment. The contribution of peripheral systems, such as the liver, in Aβ clearance, is vital, given that Aβ levels in the plasma correlate closely with those in the brain. Consequently, targeting systemic processes, rather than focusing solely on the CNS, may offer promising therapeutic approaches. Furthermore, high-density lipoprotein (HDL) facilitates the formation of lipoprotein-amyloid complexes, which are important for Aβ transport and clearance, using proteins such as apolipoproteins E and J (ApoE and ApoJ) to form complexes that help manage Aβ accumulation. On the other hand, low-density lipoprotein (LDL) facilitates Aβ efflux from the brain by binding to LRP1, promoting its clearance. Given the relationship between lipid profiles and Aβ levels, along with lipid-modifying drugs, may be effective in managing Aβ accumulation and mitigating AD progression.

01 Apr 2025·Experimental Neurology

Cellular expression of low-density lipoprotein receptor-related protein 1 and amyloid beta deposition in human and rat epileptogenic brain

Article

Author: Aronica, Eleonora ; Boonkamp, Lynn ; Broekaart, Diede W M ; Teunissen, Charlotte E ; van Vliet, Erwin A ; Idema, Sander ; Anink, Jasper J ; Gorter, Jan A ; Rozeboom, Annemieke

Decreased capillary expression of low-density lipoprotein receptor-related protein 1 (LRP1) has been linked to increased brain amyloid beta (Aβ) accumulation in Alzheimer's disease (AD). Aβ accumulation has also been observed in (a subset of) temporal lobe epilepsy (TLE) patients, suggesting a potential link between epilepsy and AD. This study examines cellular LRP1 expression in human and rat epileptogenic brain tissue to explore LRP1's role in epilepsy. LRP1 expression and localization were analyzed in hippocampal sections from patients with status epilepticus (SE, n = 12), TLE (n = 12), autopsy controls (n = 20), and AD (n = 10) using immunohistochemistry. Soluble Aβ levels and deposits were compared across TLE, AD, and control tissues. LRP1 expression was also studied in an electrical post-SE rat model of TLE. Decreased capillary LRP1 expression was found in both human and rat brain tissue (SE and TLE). Higher LRP1 expression was detected in CA1 neurons (only in human TLE) and glial cells (SE and TLE). Aβ deposits were observed in only one out of 12 TLE patients, and soluble Aβ levels were not significantly elevated. In contrast, AD patients showed decreased capillary LRP1 expression accompanied by Aβ plaques and increased soluble Aβ40/42 levels. The significant reduction in LRP1 expression in brain capillaries in both adult human and rat TLE was not clearly associated with notable Aβ accumulation implying that alternative amyloid clearance mechanisms beyond LRP1 in blood vessels might be at play. It also supports previous findings indicating that Aβ pathology may be less prominent in adult TLE than some studies suggest.

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