MORPHOLOGYBrainsinvolvedbyADshowavariabledegreeofcorticalatrophy,resultinginawideningofthecerebralsulcithatismostpronouncedinthefrontal,temporal,andparietallobes.Theatrophyproducesacompensatoryventricularenlargement(hydrocephalusexvacuo).Atthemicroscopiclevel,ADisdiagnosedbythepresenceofneuritic plaques (anextracellularlesion)andneurofibrillary tangles (anintracellularlesion)(
Fig.23.25 http://ebooksmedicine.net
Fig. 23.25 Alzheimer disease. (A) Plaques (arrow) contain a central core of amyloid and a surrounding region of dystrophic neurites (Bielschowsky stain). (B) Immunohistochemical stain for Aβ. Peptide is present in the core of the plaques as well as in the surrounding region. (C) Neurons containing tangles stained with an antibody specific for tau.
Neuritic plaques arefocal,sphericalcollectionsofdilated,tortuous,processesderivedfromdystrophicneurites,oftenaroundacentralamyloidcore(see
Fig.23.25A ).Neuriticplaquesrangeinsizefrom20to200µmindiameter;microglialcellsandreactiveastrocytesarepresentattheirperiphery.Plaquescanbefoundinthehippocampusandamygdalaaswellasintheneocortex,althoughthereisrelativesparingofprimarymotorandsensorycorticesuntillateinthediseasecourse.TheamyloidcorecontainsAβ (see
Fig.23.25B ).Aβ depositsalsocanbefoundthatlackthesurroundingneuriticreaction,termeddiffuse plaques; thesearefoundinthesuperficialcerebralcortex,thebasalganglia,andthecerebellarcortexandmayrepresentanearlystageofplaquedevelopment.
Neurofibrillary tangles arebundlesofpairedhelicalfilamentsvisibleasbasophilicfibrillarystructuresinthecytoplasmoftheneuronsthatdisplaceorencirclethenucleus;tanglescanpersistafterneuronsdie,becomingaformofextracellularpathology.Theyarecommonlyfoundincorticalneurons,especiallyintheentorhinalcortex,aswellasinthepyramidalcellsofthehippocampus,theamygdala,thebasalforebrain,andtheraphenuclei.Amajorcomponentofpairedhelicalfilamentsishyperphosphorylated tau (see
Fig.23.25C
InindividualsharboringautosomaldominantmutationsthatcauseAD,depositionofAβ andtheformationoftanglesprecedetheemergenceofcognitiveimpairmentbyasmuchas15to20years.Forthisreason,thecurrentdiagnosticcriteriaconsidertheburdenanddistributionofamyloiddeposits,tangles,andneuriticplaques—aconstellationknownasAlzheimer disease neuropathologic changes. Thestagingofeachoftheseprocesses,whichhasafairlyconsistentpatternacrossindividuals,isthenusedtoassessthelikelihoodthattheobservedlesionsresultedincognitiveimpairment.