What is a neuritic plaque?

What is a Neuritic Plaque

A neuritic plaque is a specific subtype of senile plaque characterized by extracellular β-amyloid (Aβ) deposits surrounded by dystrophic neurites that contain phosphorylated tau protein, representing a pathognomonic lesion of Alzheimer's disease that is closely associated with neuronal injury. 1

Core Structural Components

Neuritic plaques are complex lesions containing several key elements:

• Central amyloid core: Extracellular deposits of β-amyloid peptides (particularly Aβ1-40 and Aβ1-42) form the foundation of these plaques 1
• Dystrophic neurites: Swollen, degenerating neuronal processes that surround the amyloid deposits and frequently exhibit phospho-tau immunoreactivity 1
• Additional neuronal proteins: These plaques consistently contain neurofilament proteins, tau proteins, phosphotyrosine residues, and various domains of amyloid precursor proteins 2
• Inflammatory components: Activated microglia and reactive astrocytes accumulate around neuritic plaques, producing cytokines, reactive oxygen species, and proteases that contribute to local neurotoxicity 3

Critical Distinction from Other Plaque Types

Neuritic plaques must be distinguished from simple Aβ deposits or diffuse plaques using special staining techniques. 1

The preferred detection methods include:

• Thioflavin S staining or modified Bielschowsky stain to identify neuritic processes 1
• Immunohistochemical stains for amyloid precursor protein, ubiquitin, neurofilament, or phospho-tau to detect specific subtypes of dystrophic neurites 1

Clinical and Pathological Significance

Neuritic plaques represent the most consequential Aβ plaque morphology in Alzheimer's disease:

• Direct association with neuronal injury: Unlike diffuse plaques, neuritic plaques are closely linked to actual neuronal damage and dysfunction 1, 4
• Interface of pathology: These plaques sit at the convergence of Aβ deposition, tau aggregation (neurofibrillary tangles), and local immune activation 4
• Correlation with cognitive decline: Neuritic plaques are associated with neuronal network dysfunction and dementia symptoms 4

Role in Alzheimer's Disease Diagnosis

The National Institute on Aging-Alzheimer's Association guidelines incorporate neuritic plaque scoring as one of three essential parameters:

• CERAD neuritic plaque score (C score) is used alongside Aβ plaque score (A score) and Braak neurofibrillary tangle stage (B score) to create the "ABC score" 1
• "Intermediate" or "High" ABC scores that include significant neuritic plaque burden are considered sufficient explanation for dementia 1
• Neuritic plaques are scored in specific brain regions including middle frontal gyrus, superior/middle temporal gyrus, and inferior parietal lobule 1

Pathogenesis Considerations

Recent evidence suggests alternative mechanisms of neuritic plaque formation:

• Traditional view holds that diffuse Aβ deposits convert to neuritic plaques, with amyloid toxicity creating dystrophic neurites 5, 3
• Emerging evidence from preclinical human studies suggests neuritic plaques may arise from neuronal degeneration driven by iron overload and ferroptosis as the initial step, rather than Aβ toxicity alone 5
• The molecular composition of neuritic plaques remains remarkably consistent across different cortical regions and is independent of apolipoprotein E genotype 2

Common Pitfall

Do not confuse neuritic plaques with Lewy bodies—these are entirely different pathological entities. Lewy bodies are intracytoplasmic inclusions composed of aggregated alpha-synuclein found in Parkinson's disease and dementia with Lewy bodies, not extracellular amyloid deposits with dystrophic neurites. 6