Willis Lecture: Biomarkers for Inflammatory White Matter Injury in Binswanger Disease Provide Pathways to Precision Medicine

Stroke. 2022 Nov;53(11):3514-3523. doi: 10.1161/STROKEAHA.122.039211. Epub 2022 Sep 23.

Abstract

Binswanger disease is the small vessel form of vascular cognitive impairment and dementia. Deposition of Alzheimer disease proteins can begin in midlife and progress slowly, whereas aging of the vasculature also can begin in midlife, continuing to progress into old age, making mixed dementia the most common type of dementia. Biomarkers facilitate the early diagnosis of dementias. It is possible to diagnose mixed dementia before autopsy with biomarkers for vascular disease derived from diffusor tensor images on magnetic resonance imaging and Alzheimer disease proteins, Aβ (amyloid β), and phosphorylated tau, in cerebrospinal fluid or in brain with positron emission tomography. The presence of vascular disease accelerates cognitive decline. Both misfolded proteins and vascular disease promote inflammation, which can be detected in cerebrospinal fluid by the presence of MMPs (matrix metalloproteinases), angiogenic growth factors, and cytokines. MMPs disrupt the blood-brain barrier and break down myelin, producing Binswanger disease's 2 main pathological features. Advances in detecting biomarkers in plasma will provide early detection of dementia and aided by machine learning and artificial intelligence, will enhance diagnosis and form the basis for early treatments.

Keywords: Alzheimer disease; biomarkers; blood-brain barrier; matrix metalloproteinases; tomography.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides / metabolism
  • Artificial Intelligence
  • Biomarkers
  • Cerebrovascular Disorders* / pathology
  • Cognitive Dysfunction* / diagnostic imaging
  • Cytokines / metabolism
  • Dementia, Vascular* / diagnosis
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Positron-Emission Tomography
  • Precision Medicine
  • White Matter* / pathology

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Matrix Metalloproteinases
  • Cytokines