Alzheimer Neuritic Plaques

Alzheimer neuritic (senile) plaques are a diagnostic feature of Alzheimer's disease and are not seen in other neurodegenerative disorders.

Alzheimer neuritic plaques are extracellular abnormalities involving the accumulation of beta/A4-amyloid in the neuropil.  The typical mature Alzheimer neuritic plaque appears as a spherical structure measuring about 0.2 millimeters in diameter (Figure 1).  It consists of a dense central core of beta/A4-amyloid, surrounded by a halo and a ring of abnormal neurites (dystrophic neurites) associated with wisps of beta/A4-amyloid.  Although Alzheimer neuritic plaques are visible in microscopic sections stained with hematoxylin and eosin (H&E; Figure 2), they are most readily visualized in sections stained with silver impregnation techniques (e.g., the Bielschowsky stain or the Bodian stain; Figures 2 and 3).  Alzheimer neuritic plaques can also be stained with Congo Red (Figure 4) or the fluorescent dye thioflavine-S, which stains the beta/A4-amyloid (Figure 5, 6, 7, and 8).

Drawing of Alzheimer neuritic plaques

Alzheimer neuritic plaque stained with H&E (left) and silver (right)		Silver-stained Alzheimer neuritic plaque

Apple green birefringence of  Congo red-stained beta/A4-amyloid in vessel wall	Fluorescent-stained plaques (arrows) with central amyloid core

Other variations in the appearance of the plaques include: primitive (immature) plaques contain a loose accumulation of beta/A4-amyloid surrounded by abnormal neurites; diffuse plaques have a loose accumulation of beta/A4-amyloid with no surrounding abnormal neurites; and hypermature ("burned out") plaques have a dense core of amyloid surrounded by reactive astrocytes but no abnormal neurites.  Microglia (macrophages) can be found associated with most plaques.

Alzheimer neuritic plaques are often adjacent to capillaries or larger blood vessels that have accumulated beta/A4-amyloid in the vessel walls (cerebral amyloid angiopathy).

Beta/A4-amyloid in vessel wall unstained (left) and fluorescent-stained (right)
Both subarachnoid and parenchymal vessels can be involved
Many, but not all vessels are affected (compare arrows)

Alzheimer neuritic plaques are generally found throughout the cerebral cortex and are present through the entire thickness of the cortical layers (although they are sometimes more numerous in the superficial layers). Alzheimer neuritic plaques can also be found in the amygdala, substantia innominata, hypothalamus, claustrum, tegmentum of the midbrain and rostral pons, and cerebellar cortex.

Example of neuritic plaques (arrows) viewed at low power	Numerous Alzheimer neuritic plaques viewed at low power

Biochemical analysis has shown that the beta/A4-amyloid of the Alzheimer neuritic plaques derives from amyloid precursor protein (APP). The gene for this protein is located on chromosome 21. APP is a trans-membrane protein found mostly at nerve terminals. Abnormal degradation of this protein can produce peptide fragments which aggregate into the insoluble beta/A4-amyloid. Some researchers believe that the amyloid accumulation is toxic to surrounding neurons, although others believe that the amyloid accumulates as a secondary result of agonal events in the death of the neuron.

Despite some literature indicating that Alzheimer neuritic plaques can occur as a normal consequence of aging, it is most likely that the presence of neuritic plaques in the brain of a nondemented individual is an indication of the preclinical phase of the Alzheimer's disease process.