Alterations of the cerebral capillary bed in the senile dementia of Alzheimer

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Abstract
Brain tissue specimens from 15 patients dying with neuropathologically confirmed clinical diagnoses of senile dementia, Alzheimer type, and 10 approximately age and sex matched elderly patients without signs of senile change, were compared using a group of neurohistological techniques including scanning electron microscopy. In addition to previously described changes in structure of neurons and neuropil, dramatic changes were noted in the capillary bed. Normal cerebral vessels are characterized by smooth contours, the presence of occasional pericytes, and a plexus of pericapillary nerve fibers bearing many varicosities which have been shown to be strongly positive for norepinephrine, acetylcholine, dopamine and several other putative neurotransmitters or neuromodulators. In our series of Alzheimer patients the cerebral vessels were highly irregular in appearance, covered with rounded or conical extrusions (lumps and bumps), and totally lacking in the perivascular plexus of nerve fibers. In about three quarters of the cases studied the vessel walls were perforated by multiple openings of varying sizes, most of which appeared to run through the complete thickness of the thickened basement membrane but did not perforate the endothelial lining of the capillary lumen. The origin and pathogenesis of these changes is still unknown although some of the materials infiltrating the vascular walls appear to contain amyloid. On the basis of presently available evidence, it is suggested that widespread microvascular pathology may be caused by loss of the perivascular neural plexus (denervating microangiopathy) and that this may result in breakdown of the blood brain barrier. It is conceivable that the widespread degeneration characteristic of senile domentia, Alzheimer type, develops secondarily to these structuro-functional alterations in the microvasculature and that the primary target of the Alzheimer process may be located in subcortical nuclei, e.g. locus ceruleus and nucleus basalis of Meynert, which normally supply innervation to the cerebral vessels. Sono stati messi a confronto in questo studio preparati istologici cerebrali di 15 pazienti morti con diagnosi clinica di malattia di Alzheimer e di 10 individui anziani comparabili per età e sesso, morti senza presentare segni clinici di involuzione neuropsichica senile. Oltre alle già note alterazioni della struttura dei neuroni e dei neuropili sono state messe in evidenza importantissime varianti del letto capillare. Infatti, nella nostra serie di malati affetti da malattia di Alzheimer i vasi cerebrali appaiono molto irregolari con ostruzioni coniche o rotonde e sono totalmente privi di fibre nervose del plesso perivascolare. In tre quarti dei casi studiati le pareti vasali apparivano interrotte da soluzioni di continuo di varia ampiezza che interessavano totalmente la spessa membrana basale, mentre risultava indenne l’endotelio. Parte del materiale che infiltrava la parete vasale contiene sostanza amiloide. Sulla base di questi dati si può ipotizzare che questa microangiopatia denervante determini la rottura della barriera emato-encefalica e ciò fa ritenere che il primo bersaglio della malattia di Alzheimer siano il locus ceruleus e il nucleo basale di Meynert che normalmente provvedono alla innervazione dei vasi cerebrali.