Mohammed T. Abou-Saleh

NEUROPATHOLOGY OF AD 225eosin- or silver-stained sections GVD appears as numerous dotlikeparticles, each with a surrounding clear halo. These bodiesmay also be seen in ageing brains, but their number and tissuedensity are considerably greater in AD. Some granulovacuoles areimmunoreactive for ubiquitin 53,54 and they may represent residualbodies from lysosomal-mediated proteolysis 55 .Hirano BodiesThese are rod-shaped bodies, 15 mm wide and 60–100 mm long,that appear in neurones with ageing but, again, with greaterdensity in AD. They are brightly eosinophilic and immunohistochemistrysuggests they are derived from the cytoskeletalprotein, actin 56 .Neuronal loss in ADThere is conspicuous loss of neurones from the cerebral cortexand hippocampus in AD, particularly large pyramidal cells 57–59 .This loss is more marked in younger patients (580 years),although it is still significant in older individuals 59 . Golgi studiesshow loss of dendritic arborization in surviving neocortical cells 60and electron microscopy and immunohistochemistry indicateconsiderable synapse loss 61–63 . Cell loss from the nucleus basalisof Meynert, the cholinergic input into the cortex, is reflectedneurochemically by reduced choline acetyltransferase, and thatfrom the locus coeruleus can be related to a decline in corticalnoradrenaline 64 .Amyloid AngiopathyThe deposition of Ab in cerebral arteries, termed ‘‘amyloidangiopathy’’ or ‘‘congophilic angiopathy’’, is almost invariable inAD but can also exist in its own right. This amyloid angiopathymay sometimes be responsible for (lobar) cerebral haemorrhage, acause of secondary stroke in AD 65–67 .White Matter ChangesA reduction in the amount of white matter in AD is associatedwith a decrease in the intensity of myelin staining. This has beendescribed as incomplete infarction 68,69 and, although it may mimicBinswanger’s disease pathologically and on imaging, it is notassociated with lacunar infarcts or hypertensive arteriosclerosis.Such white matter changes may sometimes be related to ischaemiadue to amyloid angiopathy, but bouts of systemic hypotensionmight also be causal.REFERENCES1. Jobst K, Smith AD, Szatmari M. Detection in life of confirmedAlzheimer’s disease using a simple measurement of medial temporallobe atrophy by computed tomography. Lancet 1992; 340: 1179–83.2. Mann DMA. The topographic distribution of brain atrophy inAlzheimer’s disease. Acta Neuropathol 1991; 83: 81–6.3. Mann DMA, South PW. The topographic distribution of brainatrophy in frontal lobe dementia. Acta Neuropathol 1993; 85: 334–40.4. Varma AR, Talbot PR, Snowden JS et al. A 99 Tc-HMPAO singlephoton emission computed tomography study of Lewy body disease. JNeurol 1997; 244: 349–59.5. Hubbard BM, Anderson JN. 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