| [Objectives] To investigate several primary histomorphological changes in brain aging in Chinese: A β deposition, synaptic density changes, neuroglia changes and capillary changes. And to explore the role of vascular factor in brain aging by the detection of microvascular degeneration.[Materials and methods] Twenty-eight brains of subjects (mean age 65 years) who died without clinical or pathological involvement of nervous system and 6 brains of AD patients (mean age 83 years) were obtained at autopsy. Sections from frontal lobe, occipital lobe, stratum and hippocampus of normal s ubjects and sections from hippocampus of AD patients were used in HE, LFB, toluidine blue stains and UEA, A , SYNP, GFAP, Ferritin immunostaining. After observations of morphological changes of neuron, capillary, astrocyte, microglia and A deposition, computer image analysis was performed to quantify average optical density of SYNP immunoreactivity, numerical density and area density of neuron and capillary in frontal lobe, occipital lobe, putamen, CA3 sector of normal subjects and CA3 sector of AD patients. Numerical ratio and area ratio of neuron and capillary were then calculated. Correlations between each variable and age were estimated using Pearson's correlation test. Differences of variables in CA3 sector between AD patients and advanced aged normal subjects (>75 years) was analyzed with Student's t-test.[Results]1. Several pathological microvascular changes were seen in aged subjects and more prevalent in AD patients: increased tortuosity, looping, bundling, stringing, and effacement of endothelia. Numerical ratio and area ratio of neuron and capillary of frontal lobe, occipital lobe and putamen significantly increased with age in normal aging subjects.2. In normal aging subjects, A depositions were seen in half (9cases) of those over age of 70, and absent in other brains up to age of 90. Various forms (diffuse, primitive, mature, and burn-out) of plaques were seen in gray matter of 8 cases, with the most frequently involvement of frontal lobe and the least frequently involvement of hippocampus. Burn-out plaque like A depositions were also found in white matter in two cases. CAA appeared in 7 cases, in CA, PA and mixed pattern separately. Numerous A depositions were found in hippocampus of AD patients, including plaques and CAA.3. GFAP positive astrocytes and ferritin positive microglia predominantly distributed in white and gray matter, separately. Proliferation and hypertrophy of these neuroglia cells were seen to some extent in most normal aged brains, and marked in AD patient. Clusters of activated microglia were seen in cortices of some normal subjects who had plaques, and in hippocampus of AD patients.4. SYNP reactivity in frontal lobe, occipital 1 obe, putamen and CAS sector of hippocampus negatively correlated with age in normal aging subjects. Significant difference in SYNP reactivity of CA3 sector was found between AD patients and normal subjects over age of 75.[Conclusions]1. Morphological changes and relative decrease in number and capacity of capillary in aging brain may reduce cerebral blood flow and metabolism, andconsequently result in functional impairment of aging brain. Vascular factors may play an important role in the development of brain aging.2. A deposition was rarely seen in normal subjects before seventy, while commonly but unnecessarily seen in those with advanced age. A may also deposit in white matter of aged brains. Different mechanisms may be involved in the development of different patterns of CAA.3. Activations of astrocyte and microglia participate in brain aging. The increase of activated microglia may be related to microvascular degeneration and may take part in the formation of senile plaques. Ferritin immunohistochemistry is suitable for the detection of microglia in archived paraffin-embedded brain blocks.4. Decrease of synaptic density was prevalent in aging brains.
|
PDF Full Text Request