HomeGeneticsConditionAdult-onset leukoencephalopathy with axonal spheroids and pigmented glia
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Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

ALSP is a rare neurological condition characterized by white matter damage, axonal spheroids, and pigmented glial cells, typically manifesting in a person's forties.

Overview

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurological condition characterized by changes to certain areas of the brain. A hallmark of ALSP is leukoencephalopathy, which is the alteration of a type of brain tissue called white matter. White matter consists of nerve fibers (axons) covered by a substance called myelin that insulates and protects them. The axons extend from nerve cells and transmit nerve impulses throughout the body. Areas of damage to this brain tissue (white matter lesions) can be seen with magnetic resonance imaging (MRI).

Another feature of ALSP is swellings called spheroids in the axons of the brain, which are a sign of axon damage. Also common in ALSP are abnormally pigmented glial cells. Glial cells are specialized brain cells that protect and maintain neurons. Damage to myelin and neurons is thought to contribute to many of the neurological signs and symptoms in people with ALSP.

Symptoms

Symptoms of ALSP usually begin in a person's forties and worsen over time. Key features include:

  • Personality changes: Including depression and a loss of social inhibitions.
  • Cognitive decline: Memory loss and loss of executive function (the ability to plan, implement actions, and develop problem-solving strategies). This impairs skills such as impulse control, self-monitoring, and focusing attention.
  • Dementia: As the condition progresses, it causes a severe decline in thinking and reasoning abilities.
  • Seizures: Some people experience mild seizures, usually only when the condition begins.
  • Motor skill impairment: Difficulty walking and movement abnormalities known as parkinsonism.

Parkinsonism includes:

  • Bradykinesia: Unusually slow movement.
  • Tremor: Involuntary trembling.
  • Rigidity: Muscle stiffness.

The pattern of cognitive and motor problems is variable, even among individuals in the same family, although almost all affected individuals ultimately become unable to walk, speak, and care for themselves.

Causes

ALSP is caused by mutations in the CSF1R gene. This gene provides instructions for making a protein called colony stimulating factor 1 receptor (CSF-1 receptor), which is found in the outer membrane of certain types of cells, including glial cells. The CSF-1 receptor triggers signaling pathways that control many important cellular processes, such as cell growth, division (proliferation), and maturation (differentiation).

Mutations in the CSF1R gene lead to an altered protein that is likely unable to stimulate cell signaling pathways. However, it is currently unclear how these mutations lead to white matter damage or the specific cognitive and movement problems observed in patients.

Inheritance

This condition is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from a parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Frequently Asked Questions

There is currently no cure for ALSP, as it is a progressive genetic disorder. Management is strictly supportive and focuses on symptom control. This includes the use of anticonvulsant medications to manage seizures, which are common in the early stages, and psychiatric medications to address mood disorders or behavioral changes. Physical and occupational therapy are also critical to maintain mobility and independence for as long as possible, while caregivers receive support to manage the increasing care needs as the disease progresses.
Diagnosis relies heavily on genetic testing for mutations in the CSF1R gene, which is the definitive marker for ALSP. While MRI scans show white matter lesions in both ALSP and multiple sclerosis (MS), the pattern in ALSP is typically more symmetric and involves specific areas like the frontal and parietal lobes, often sparing the periventricular regions seen in MS. Additionally, ALSP patients usually lack the inflammatory markers found in cerebrospinal fluid samples of MS patients, and the clinical progression in ALSP is consistently degenerative rather than the relapsing-remitting course typical of MS.
LSP follows an autosomal dominant inheritance pattern, meaning that a single copy of the mutated gene is sufficient to cause the disorder. If one parent has ALSP, each child has a 50 percent chance of inheriting the mutation. However, the condition is not always fully penetrant, meaning some individuals who carry the mutation may not develop symptoms or may have a milder course. Genetic counseling is recommended for family members to understand the risks and to discuss options for genetic testing, particularly for adult children who may be at risk.
Early signs often include a distinct change in personality, such as a loss of social inhibitions, apathy, or depression, which may appear before significant memory loss. Unlike typical dementia where memory is the primary deficit, ALSP often presents with executive dysfunction, meaning the patient struggles with planning, organizing, and impulse control. Family members may notice that the individual becomes socially awkward or inappropriate in their interactions, and these behavioral changes are often more prominent than early memory complaints.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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