Topographical distribution of cerebral amyloid angiopathy and its effect on cognitive decline are influenced by Alzheimer disease pathology
Introduction
Cerebral amyloid angiopathy (CAA) is defined as deposition of a congophilic material i.e. β-amyloid peptide (Aβ) in meningeal and cortical (parenchymal) arteries, arterioles, capillaries, and veins [1], [2], [3], [4], [5], [6], [7], [8], [9]. Familial CAA refers to CAA occurring in a variety of familial disorders associated with mutations of the amyloid precursor protein [9], [10], [11], [12], [13], [14]. However, CAA much more frequently occurs as a sporadic, non familial disease. In the present paper the term CAA refers to sporadic CAA, which is a common finding in the brains of elderly demented and non-demented individuals and which is associated with Alzheimer disease (AD) as its prevalence varies from 70% to 100% in AD [1], [4], [6], [8], [15], [16], [17], [18], [19], [20], [21], [22], [23]. Independent of AD, both incidence and severity of CAA increase with age [1], [6], [9], [14], [17], [24], [25], [26], [27]. Severe CAA is associated with cerebral hemorrhages, infarctions, and white matter lesions [1], [2], [6], [9], [14], [26], [28], [29], [30], [31], [32] (for review on CAA see [26], [33]).
The origin of Aβ in CAA remains unclear. Basically, three different mechanisms have been proposed (see [26]): derivation of Aβ from blood and/or cerebrospinal fluid [9], [34], [35], production of Aβ by smooth muscle cells within vessel walls and/or pericytes [9], [36], [37], [38], [39], [40], and derivation of Aβ from the neuropil in the course of its perivascular drainage [2], [7], [41], [42], [43], [44], [45].
CAA seems to be most prominent in occipital, frontal, and temporal lobes, followed by parietal lobe and white matter, whereas basal ganglia and thalamus are usually spared [1], [3], [4], [9], [19], [42], [43], [45], [46]. Its occurrence in the cerebellum ranges from absent to frequent [16], [42].
Despite its association with AD, CAA has been shown recently to be an independent risk factor for cognitive decline [3], [27], [32], [47], [48].
However, data on both topographical distribution of CAA and its impact on cognitive decline are rare [19], [20], [46], [49], [50]. The aim of the present study was to further evaluate the influence of neuritic AD pathology (ADP; e.g., CERAD scores [51], Braak stages [52], NIA-Reagan Institute Criteria [53]) on the association between CAA and clinical dementia and on severity and topographical distribution of CAA, respectively.
Section snippets
Materials and methods
We examined 171 human brains obtained at autopsy in the pathological department of a large hospital in Vienna, Austria. The patients' age ranged from 54 to 104 years (mean: 83.9 years, SD:+/− 9.18), 102 were female (59.6%) and 96 were clinically demented (56.1%). Dementia was assessed retrospectively from hospital charts according to ICD-10 criteria or MMSE < 20.
Tissue was fixed in 8% aqueous solution of formaldehyde; blocks were taken from frontal, frontobasal, temporal, and occipital cortices,
Results
Our cohort consisted of 66 (38.6%) brains with high grade (CERAD B, C; Braak stages 5,6; NIA-RI Criteria high probability), 25 (14.6%) with medium grade (CERAD A, B; Braak stages 3, 4; NIA-RI Criteria medium probability), 42 (24.6%) with low grade (CERAD negative, A; Braak stages 1, 2; NIA-RI Criteria low probability), and 38 (22.2%) without ADP (CERAD negative; Braak stages 0, 1; NIA-RI Criteria negative), respectively. High grade ADP was seen in 16% of clinically non-demented patients and in
Discussion
CAA was present in 68.4% of the whole study cohort and in 86.4% of cases with neuropathology indicative for definite AD (i.e., NIA-RI Criteria high probability). These data are in accordance with CAA prevalence rates of 80% to almost 100% [1], [26], [40], [54] in AD, but are somewhat higher than the 10% to 40% prevalence rates reported in the general elderly population [1], [3], [4], [17], [27], [44].
CAA was both most frequent and most severe in the occipital lobe, followed by frontal,
Acknowledgements
The authors are grateful to Nutricia Corp. for providing financial support for M. Quass and thanks to Mrs. Veronika Rappelsberger and Mrs. Barbara Weidinger for their excellent laboratory work. Part of the study was supported by the Society for Support of Research in Experimental Neurology, Vienna, Austria.
References (62)
- et al.
Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia
Am J Pathol
(2001) - et al.
Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease
Am J Pathol
(2001) - et al.
Negative association between amyloid plaques and cerebral amyloid angiopathy in Alzheimer's disease
Neurosci Lett
(2003) - et al.
Blood–brain barrier transport of circulating Alzheimer's amyloid beta
Biochem Biophys Res Commun
(1993) - et al.
Amyloid beta precursor protein-mRNA is expressed throughout cerebral vessel walls
Brain Res
(1999) - et al.
Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease
Am J Pathol
(1998) - et al.
Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer's disease; Pro-CAA position statement
Neurobiol Aging
(2004) - et al.
Vascular pathologies and cognition in a population-based cohort of elderly people
J Neurol Sci
(2004) - et al.
Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer disease
J Neurol Sci
(2005) Alzheimer disease and cerebrovascular pathology: an update
J Neural Transm
(2002)