Simple Molecule L10 Reverses Alzheimer’s-like Symptoms in Rats by Removing Excess Copper

Researchers have identified a simple chemical compound, called L10, that reverses several Alzheimer’s-like deficits in a rat model by removing excess copper from beta-amyloid deposits. The compound reduced neuroinflammation and oxidative stress and improved spatial memory in treated animals, prompting the team to pursue further testing toward human trials.

Why copper and beta-amyloid matter

A hallmark of Alzheimer’s disease is the accumulation of beta-amyloid plaques in the brain. Although it remains unclear whether these plaques cause cognitive decline or are a by-product, many therapies target them because current drugs only ease symptoms rather than address underlying disease processes.

Over the past decade, studies have suggested that copper ions can promote the aggregation of beta-amyloid. Changes in genes or enzymes that control cellular copper transport may lead to excess copper in the brain, which in turn can favor plaque formation and increase oxidative damage.

“It was discovered that genetic mutations and changes in enzymes that act in the transport of copper in cells could lead to the accumulation of the element in the brain, favoring the aggregation of these plaques,” says biochemist Giselle Cerchiaro of the Federal University of the ABC (UFABC) in Brazil. “Thus, the regulation of copper homeostasis has become one of the focuses for the treatment of Alzheimer's.”

How the compound was identified and tested

The research team screened nine candidate molecules — eight imines (organic compounds with a carbon–nitrogen double bond) and one quinoline-based compound — to find agents that could selectively chelate (bind and remove) excess copper from beta-amyloid plaques. An initial in silico (computer) screen shortlisted two imines, labeled L09 and L10, and the quinoline compound, L11, as likely to cross the blood–brain barrier and be orally deliverable.

In cultured mouse brain cells, L11 proved cytotoxic and appeared to increase oxidative stress, while L09 and L10 displayed relatively low toxicity and protected lipids and DNA from oxidative damage associated with beta-amyloid. Based on these findings, the team advanced the compounds to animal testing.

To model Alzheimer’s-like pathology, rats received injections of streptozotocin, a compound that impairs insulin-producing cells and induces brain changes including beta-amyloid accumulation. In this model, L10 emerged as the best-performing candidate: it normalized copper levels in the hippocampus (a key memory region), significantly reduced markers of neuroinflammation and oxidative stress, and improved performance in a spatial-maze memory test. L09 and L11 produced substantially weaker or adverse effects across these measures.

Implications and next steps

The investigators describe L10 as a simple, inexpensive molecule with potential therapeutic value for the subset of Alzheimer’s patients whose brains exhibit copper accumulation. They are planning further preclinical work and hope to advance to clinical trials to assess safety and efficacy in humans.

Important caveats: the results are preclinical and based on a specific rat model; streptozotocin-induced changes approximate some aspects of Alzheimer’s but do not replicate the full complexity of human disease. The compound may be relevant only to patients whose pathology involves copper imbalance, since some people with Alzheimer’s have low, not high, brain copper. Extensive additional testing — including dose-finding, long-term safety, and human clinical trials — is required before any clinical use.

The study is published in ACS Chemical Neuroscience.