Alzheimer’s Disease Pathology

Alzheimer’s disease gross and light microscopic features

Gross – variable degree of cortical atrophy with widening of the cerebral sulci that is msot pronoucned in the frontal, temporal, and parietal lobes

- with significant atrophy, there is compensatory ventricular enlargement secondary to loss of parenchyma

LM – neurofibrillary tangles, senile (neuritic) plaques, amyloid angiopathy

- neurofibrillary tangles:  bundles of filaments in the cytoplasm fo the neurons that displace or encircle the nucleus

- often have an elongated “flame” shape

- in some cells, the basket weave of fibers around the nucleus takes on a rounded contour (globose tangles)

- visible as basophilic fibrillary structures with H&E staining but dramatically demonstrated by silver (Bielschowsky) staining

- commonly found in cortical neurons, especially in the entorhinal cortex, as well as in otehr sites such as pyramidal cells of the hippocampus, the amygdala, the basal forebrain, and the raphe nuclei

- tangles insoluble and apparently difficutl to proteolyzxe in vivo, thus remaining visible in tissue sections as “ghost” or “tombstone” tangles long after the death of the parent neuron

- stain with tau, ubiquitin, amyloid b-peptide (Ab)

- neuritic plaques:  focal, spherical collections of dilated, tortuous, silver-staining neuritic processes (dystrophic neurites) surrounding a central amyloid core, often surrounded by clear halo

- range in size from 20-200 mm in diameter

- microglial cells and reactive astrocytes present at their periphery

- found in hippocampus and amygdala as well as in neocortex

- usually relative sparing of primary motor and sensory cortices (this also applies for neurofibrillary tangles)

- amyloid core can be stained by Congo red and Bielschowsky silver methods

- amyloid core contains several abnormal proteins, stains with Ab

- Ab immunostaining demonstrates existence, in some patients fo amyloid peptide deposits of lesions lacking the surrounding neuritic reaction

- these lesions called diffuse plaques, found in superficial portison fo cerebral cortex as well as in basal ganglia and cerebellear cortex

- commonly when diffuse plaques found in cerebral cortex, they appear to be centered on small vessels or on clusters of neurons

- diffuse plaques may represent early stage of neuritic plaque development

- amyloid angiopathy almost always present

- vascular amyloid derived from same precursor as amyloid cores of plaques (APP)

- granulovacuolar degeneration:  formation of small (5 mm) clear intraneuronal cytoplasmic vacuoles, each of which contains an argyrophilic granule

- found in great abundance in hippocampus and olfactory bulb in Alzheimer’s

- Hirano bodies:  elongated glassy eosinophilic bodies consisting of paracrystalline arrays of beaded filaments, with actin as major component

- found most commonly along hippocampal pyramidal cells

Alzheimer’s disease clinical features

initially – forgetfulness and other memory disturbances

- insidious impairment of higher intellectual function

- alterations in mood and behaviour

with progression – language deficits (aphasia)

- disorientation

- loss of mathematical skills

- loss of learned motor skills

final stages – incontinence

- muteness

- inability to walk

common terminal event – pneumonia

Alzheimer’s disease pathogenesis

- see above

Alzheimer’s disease gross features of the brain

- cortical atrophy

- widening of cerebral sulci (most severe in frontal, temporal, parietal lobes)

- ventricular enlargement

Alzheimer’s disease microscopic features of the brain

- neurofibrillary tangles

- senile (neuritic) plaques

- amyloid angiopathy

- diffuse plaques

- granulovacuolar degeneration

- Hirano bodies

Diagnostic criteria

- neurofibrillary tangles, senile (neuritic) plaques, amyloid angiopathy can all be seen to a lesser extent in brains fo elderly nondemented individuals

- diagnosis of Alzheimer disease based on a combination of clinical and pathologic features

- several different methods proposed, which include evaluation of different regions of the brain and various methods for estimating the frequency of plaques and tangles

References:

1. Robbins & Cotran Pathologic Basis of Disease, 8th edition. Vinay Kumar, MBBS, MD, FRCPath; Abul K. Abbas, MBBS; Nelson Fausto, MD; Jon Aster, MD. Saunders. Published June 2009.

2. Sternberg’s Diagnostic Surgical Pathology, 5th edition. Darryl Carter, Joel K. Greenson, Victor E. Reuter , Mark H. Stoler. Lippincott Williams & Wilkins. Published Aug 26 2009.