Affiliations: [a] Laboratory of Neuropathology, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [b] Laboratory of Neuropathology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Correspondence:
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Corresponding author: Dr. de la Monte, Rhode Island Hospital, Brown University School of Medicine, 55 Claverick Street, Room 419, Providence, RI 02903, USA, Tel.: +1 401 444 7364; Fax: +1 401 444 2939; E-mail: [email protected].
Abstract: We report an unusual case of amyotrophic lateral sclerosis (ALS) marked by extensive cerebral amyloid-β deposition in small and medium-size vessels, capillaries, and perivascular plaques in the cerebral cortex, and in most leptomeningeal vessels. Despite considerable cerebral amyloidosis, the patient remained cognitively intact until death. For comparison with other neuro-degenerative diseases and normal aging, we assessed the densities of amyloid-β-immunoreactive cortical vessels and plaques in matched frontal and temporal lobe sections from archival uncomplicated cases of Alzheimer's disease (N = 10), Pick's disease (PkD; N = 4), Parkinson's disease (PD; N = 6), Diffuse Lewy body disease (DLBD; N = 7), progressive supranuclear palsy (PSP; N = 5), multiple systems atrophy (MSA; N = 4), ALS (N = 7), or normal aging (N = 10) by semi-quantitative grading (0 to 3+). Moderate (2+) or abundant (3+) cerebrovascular amyloid-β immunoreactivity was detected in 8/10 AD, 3/7 DLBD, 3/6 PD, 1 each with PSP or PkD, and 2/10 controls. Moderate or abundant densities of amyloid-β-immunoreactive diffuse plaques were detected in all cases of AD or DLBD, 4/6 with PD, 3/5 with PSP, and 2/10 controls. Moderate or abundant amyloid-β-immunoreactive mature (dense core) plaques were present in all cases of AD or DLBD, and 3 each with PD or PSP. Importantly, amyloid-β-immunoreactivity was not observed in the 4 MSA or 7 archival ALS cases. This study demonstrates that prominent amyloid-β accumulation in cerebral vessels and plaques occurs frequently in AD, DLBD, PSP, and PD, but not in ALS or MSA, indicating that the case described is unique. The lack of cognitive impairment in the case presented argues against the idea that extensive amyloid-β deposition in the brain causes dementia.
