Cerebral Beta Amyloid Angiopathy Is a Risk Factor for Cerebral Ischemic Infarction. A Case Control Study in Human Brain Biopsies

Cerebral amyloid angiopathy (CAA) is conspicuous for its association with Alzheimer disease (AD) and as a cause of lobar hemorrhages in the elderly, but its role in cerebral infarction is less clear. There is evidence that CAA may also be a risk factor for ischemic infarction in AD. To further investigate CAA as a risk factor for infarction, we studied 108 cases of recent cerebral or cerebellar infarction diagnosed in tissue samples obtained from surgical material. There were 69 males and 39 females with a mean age of 52 yr (range 1–86). The majority of biopsies were obtained from the frontal and parietal lobes. Radiological studies demonstrated a lesion confined to a vascular distribution in 12 of the 17 (71%) cases examined. Microscopic sections stained with hematoxylin and eosin revealed complete, organizing infarction in 107 cases with areas of coagulative necrosis, anoxic-ischemic neuronal injury, inflammation, macrophages, vascular proliferation, gliosis, and swollen axons. One case showed an incomplete infarct. Most cases also exhibited a minor hemorrhagic component with hemosiderin and hematoidin pigments. CAA, defined as amyloid deposition in the walls of leptomeningeal and parenchymal arteries, was found by immunohistochemical stains for beta amyloid in 14 (13%) cases of complete cerebral infarct. Cortical beta amyloid plaques were found by immunohistochemistry in 19 (17%) cases. Cerebral or cerebellar tissues containing cortex and leptomeninges obtained from 136 patients with a mean age of 52 yr (range 1–85) during surgical procedures for diagnosis of primary or metastatic neoplasms and demyelinating lesions were used as age-matched controls. In this control group, CAA was found in 5 (3.7%) and beta amyloid plaques in 19 (14%). The results indicate that CAA, but not beta amyloid plaque formation, is significantly more common in patients with ischemic cerebral infarction than in age-matched controls with non-vascular lesions (odds ratio 3.8; 95% confidence interval 1.3–10.9; p < 0.01). Our results indicate that CAA is a risk factor for ischemic cerebral infarction in the population studied.

[1]  Yu-Min Kuo,et al.  Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. , 1998, The American journal of pathology.

[2]  R. Roos,et al.  Microvasculopathy is associated with the number of cerebrovascular lesions in hereditary cerebral hemorrhage with amyloidosis, Dutch type. , 1998, Stroke.

[3]  J. H. Kim.  Neuropathology: The Diagnostic Approach , 1998 .

[4]  J. Nicoll,et al.  High frequency of apolipoprotein E ϵ2 allele is specific for patients with cerebral amyloid angiopathy-related haemorrhage , 1998, Neuroscience Letters.

[5]  C. Iadecola,et al.  Increased Susceptibility to Ischemic Brain Damage in Transgenic Mice Overexpressing the Amyloid Precursor Protein , 1997, The Journal of Neuroscience.

[6]  R. Katzman.,et al.  Types of cerebrovascular lesions associated with severe cerebral amyloid angiopathy in Alzheimer's disease. , 1997, Annals of the New York Academy of Sciences.

[7]  D. Graham,et al.  High frequency of apolipoprotein E ϵ2 Allele in hemorrhage due to cerebral amyloid angiopathy , 1997, Annals of neurology.

[8]  L. Walker,et al.  Cystatin C. Icelandic-like mutation in an animal model of cerebrovascular beta-amyloidosis. , 1996, Stroke.

[9]  John X. Morris,et al.  The diagnosis of Alzheimer's disease. , 1999, Journal of Alzheimer's disease : JAD.

[10]  H. Vinters,et al.  Brain Parenchymal and Microvascular Amyloid in Alzheimer's Disease , 1996, Brain pathology.

[11]  R. Roos,et al.  Hereditary Cerebral Hemorrhage with Amyloidosis‐Dutch Type (HCHWA‐D): I ‐ A Review of Clinical, Radiologic and Genetic Aspects , 1996, Brain pathology.

[12]  D. Premkumar,et al.  Apolipoprotein E Alleles and Brain Vascular Pathology in Alzheimer's Disease a , 1996, Annals of the New York Academy of Sciences.

[13]  B. Hyman,et al.  Apolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy , 1995 .

[14]  L. Thal,et al.  Cerebral infarction in Alzheimer's disease is associated with severe amyloid angiopathy and hypertension. , 1995, Archives of neurology.

[15]  W. Saeger,et al.  Cerebral amyloid angiopathy. Frequency, significance and immunohistochemistry. , 1993, Zentralblatt fur Pathologie.

[16]  S. Mirra,et al.  Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists. , 1993, Archives of pathology & laboratory medicine.

[17]  K. John.  The Diagnostic Approach , 1986 .

[18]  T. Mandybur.  Cerebral Amyloid Angiopathy: The Vascular Pathology and Complications , 1986, Journal of neuropathology and experimental neurology.

[19]  H. Vinters,et al.  Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. , 1983, Stroke.

[20]  H. Vinters,et al.  Cerebral amyloid angiopathy: incidence and complications in the aging brain. I. Cerebral hemorrhage. , 1983, Stroke.

[21]  M. Tomonaga,et al.  Cerebral Amyloid Angiopathy in the Elderly , 1981, Journal of the American Geriatrics Society.

[22]  J. Nicoll,et al.  High frequency of apolipoprotein E epsilon 2 allele is specific for patients with cerebral amyloid angiopathy-related haemorrhage. , 1998, Neuroscience letters.

[23]  B. Hyman,et al.  Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. , 1995, Annals of neurology.

[24]  R. Campbell,et al.  Clinicopathologic studies of primary cerebral amyloid angiopathy. , 1979, Mayo Clinic proceedings.

[25]  K S Mathur,et al.  Vascular diseases. , 1970, The Journal of the Association of Physicians of India.