Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology

Plaque-like lesions and amyloid angiopathywere investigated in the frontal cerebral cortex of four patients with hereditary cerebral hemorrhagewith amyloidosis (Dutch) (HCHWA-D), using immunohistochemical [antibodies to β amyloid protein (Aβ), β protein precursor(βPP), synaptophysin, ubiquitin (UBQ), cathepsin D, paired helical filaments (PHF) and glial fibrillary acidic protein(GFAP)], enzymehistochemical ( acid phosphatase) and silver [ methenaminesilver (MS) and Palmgren] staining methods. Whereas Aβ-and MS-positive diffuse plaques were found in all patients, only the three older patients showed neuriticor congophilic plaques, which were acid phosphataseand cathepsin Dpositive and contained βPP-, synaptophysin-and UBQ-positive, but PHF-negative neurites. These plaques were surrounded by reactive astrocytes. Similar immuno-and enzymereactivity was found around congophilic blood vessels. Thus, apart from neuronal degeneration in a subset of plaque-like lesions and around blood vessels, this study shows an age-related morphology of the plaques in HCHWA-D, corresponding to that in Down's syndrome (DS), with the difference that neurofibrillary (NF) pathology is absent in HCHWA-D in contrast to DS. HCHWA-D may be considered as a model for congophilic plaque formation not associated with NF pathology.