ABSTRACT
Cerebral amyloid angiopathy (CAA) is defined by beta-amyloid peptide (Abeta) depositions in cerebral vessels and is associated with Alzheimer disease (AD). It has been suggested that severe CAA is an independent risk factor for cognitive decline. 171 autopsy brains underwent standardized neuropathological assessment, the patients age ranged from 54 to 104 years (mean age: 83.9 years, +/-9.2, 59.6% female, 56.1% clinically demented). Using immunohistochemistry, the severity of Abeta depositions in vessels was assessed semiquantitatively in the frontal, frontobasal, hippocampal, and occipital region, respectively. CAA was present in 117 cases (68.4%), with the occipital region being affected significantly stronger than other regions. The overall incidence of CAA was significantly higher in cases with high grade neuritic AD pathology (ADP) compared to those with low grade or no ADP. The severity of CAA significantly increased with increasing ADP, with CAA in the occipital region increasing significantly stronger than that in other regions. The association of CAA and clinical dementia failed to remain statistically significant when adjusting for concomitant ADP. However, in cases devoid of any ADP CAA was significantly associated with the presence of clinical dementia. These results indicate a strong association of AD with CAA, but do not unequivocally support reports suggesting CAA to be an independent risk factor for cognitive decline, except for a subgroup of demented patients lacking any ADP.
Subject(s)
Alzheimer Disease/pathology , Cerebral Amyloid Angiopathy/pathology , Cerebral Arteries/pathology , Cognition Disorders/pathology , Telencephalon/pathology , Aged , Aged, 80 and over , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Cerebral Amyloid Angiopathy/physiopathology , Cerebral Amyloid Angiopathy/psychology , Cerebral Arteries/physiopathology , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Cohort Studies , Disease Progression , Female , Humans , Immunohistochemistry , Male , Microcirculation/pathology , Microcirculation/physiopathology , Middle Aged , Occipital Lobe/blood supply , Occipital Lobe/pathology , Occipital Lobe/physiopathology , Plaque, Amyloid/metabolism , Plaque, Amyloid/pathology , Risk Factors , Telencephalon/blood supply , Telencephalon/physiopathologyABSTRACT
Extrapyramidal symptoms (EPS) in Alzheimer disease (AD) often increase with disease severity. Their neuropathological substrate is a matter of discussion. We investigated tau and alpha-synuclein (AS) pathologies in brainstem in AD patients with and without EPS. Among 160 elderly subjects with autopsy-proven AD (110 female, 50 male, aged 61-102, mean 84.1 +/- 8.3 SD years), 151 (94.4%) being demented, 35 (21.9%) had clinically reported EPS (rigidity, bradykinesia, gait impairment). Neuropathological examination included standardized classification of AD according to current criteria, and semiquantitative assessment of neuronal loss in substantia nigra (SN), locus coeruleus (LC), and of tau and AS lesions in brainstem, and, in addition, of cerebrovascular lesions. The prevalence of EPS was only slightly more frequent in higher Braak stages. Tau pathology in brainstem significantly increased with increasing Braak stages, while AS lesions did not. EPS correlated best with SN cell loss (P < 0.001) and much less with AS pathology in several brain areas (P < 0.05), except in medulla oblongata (P < 0.001). Although both pathologies in substantia nigra correlated with neuron loss (P < 0.001), nigral tau lesions, present in 88.5% of EPS positive cases (without AS lesions in 55.6%), did not correlate with EPS. Additional cerebrovascular changes apparently did not influence the development of EPS symptoms in fully developed AD. With other recent data, these results suggest that neuronal loss in SN, partly related to tau lesions, is a major pathological substrate of EPS in AD, but some cases with and without EPS may show no or only minimal nigral changes. However, often associated with nigral tau lesions and higher Braak stages, EPS in elderly patients may be a surrogate marker for severe neuritic AD pathology.
Subject(s)
Alzheimer Disease/metabolism , Basal Ganglia Diseases/etiology , Brain Stem/metabolism , alpha-Synuclein/metabolism , tau Proteins/metabolism , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Female , Humans , Male , Middle Aged , Nerve Degeneration/pathology , Psychiatric Status Rating Scales , Retrospective Studies , Statistics, NonparametricABSTRACT
Disturbed calcium homeostasis plays a crucial role in the aetiology of Alzheimer's disease (AD) and the aging process. We evaluated immunoreactivity of secretagogin, a recently cloned calcium binding protein, in hippocampus and adjacent entorhinal cortex of 30 neuropathologically examined post mortem brains (m:f=12:18; mean age, 79.8+/-15.1 years). The study group consisted of 15 cases fulfilling the criteria for high probability of AD according to the NIA-Reagan Institute Criteria and 15 cases with no to medium probability. Sections were incubated with secretagogin-specific antibodies and the number of immunoreactive neurons as well as staining intensities in both neurons and neuropil were assessed. Both cellular and neuropil immunoreactivity were restricted to subiculum and Ammons horn. Cellular immunoreactivity was further restricted to pyramidal neurons and showed a hierarchical distribution: the mean percentage of immunoreactive neurons was highest in sector CA3 (64.41%), followed by CA2 (44.09%), CA4 (34.38%), CA1 (10.9%), and the subiculum (2.92%; P<0.001, except CA2-CA4, P>0.05), while it did not differ significantly between groups with different degrees of AD pathology. The pattern of secretagogin immunoreactivity resembles that of calcium sensor proteins as it is restricted to a subset of neurons and therefore secretagogin could serve highly specialized tasks in neuronal calcium signalling.
