Alzheimer’s research points to possible new brain-fluid indicator

Researchers in Spain have identified increased levels of an active enzyme in the brain and cerebrospinal fluid of people with Alzheimer’s disease, raising the possibility of a new indicator of the condition.

The enzyme, known as meprin-β, is involved in one of the processes through which beta-amyloid is produced. Beta-amyloid accumulation is one of the defining features associated with Alzheimer’s.

SciTechDaily reports that the research focused on whether meprin-β may have a role alongside BACE1, the enzyme that has traditionally received much of the attention in this area of Alzheimer’s research.

The study was led by Javier Sáez Valero at the Altered Molecular Mechanism in Alzheimer’s Disease and Dementia laboratory at the Institute for Neurosciences, a joint centre of Miguel Hernández University of Elche and the Spanish National Research Council.

The findings were published in Alzheimer’s Research & Therapy.

Researchers examined human brain samples and cerebrospinal fluid, distinguishing between immature meprin-β, which is inactive, and its mature, active form.

They found increased levels of active meprin-β in brain samples from people with Alzheimer’s, particularly at more advanced Braak stages, a scale used to describe the progression of disease-related changes.

Higher levels of MEP1B messenger RNA were also detected during intermediate and advanced stages.

The researchers then used human neurons developed from induced pluripotent stem cells to examine the relationship between beta-amyloid and the enzyme.

When the neurons were exposed to Aβ42, a form of beta-amyloid, levels of meprin-β increased significantly.

A related experiment involving genetically modified rats with Alzheimer’s-like changes also found higher levels of active meprin-β in cerebrospinal fluid.

The findings do not establish that meprin-β causes Alzheimer’s. Instead, the experiments point to a relationship between beta-amyloid accumulation and changes in the enzyme.

The presence of elevated active meprin-β in cerebrospinal fluid is of particular interest because the fluid can be obtained through lumbar puncture and tested for biological markers associated with processes in the nervous system.

The researchers say further work is needed to establish whether meprin-β could ultimately be used as an indicator of Alzheimer’s disease.