CLINICOPATHOLOY OF DEMENTIA SYMPTOMS N ALZHEIMER'S DISEASE : A MORPHOMETRIC STUDY IN THE HIPPOCAMPAL LESIONS

海马皮层（海马形成区和海马旁回）是记忆系统的关键结构，是阿尔茨海默病（AD）中受影响最大的区域。为了更充分地探讨阿尔茨海默病海马皮层神经原纤维变性引起的记忆障碍和神经元死亡等痴呆症状之间的临床病理关系，采用Gallyas苏木精-伊红染色对22例不同病程患者海马皮层8个亚区未受影响的神经元、细胞内神经原纤维缠结（i- nft）和细胞外神经原纤维缠结（e- nft）进行形态测量。检查的细分包括CA1-4、前隐骨（PRO）、下隐骨和前隐骨（PRE）、副隐骨（PARA）和内嗅皮质（ENT）。除PRE外，AD患者中未受影响的神经元密度与e-NFT密度和总NFT密度呈显著负相关。特别是在CA2、CA1、PRO和ENT中，神经元密度与这些NFT密度之间存在较强的相关性。CA1和ENT中未受影响的神经元和e-NFT密度均与病程显著相关。i/e-NFT比率是衡量神经原纤维变性导致的神经元死亡程度和/或进展速度的指标，在AD患者的耳鼻炎中显示最低。研究结果表明，耳鼻喉科由神经原纤维变性引起的神经元死亡开始最早和/或进展最快。此外，ENT和CA1的i/e-NFT比值与疾病持续时间显著相关，表明这两个分支的持续神经元死亡模式与AD的疾病进展相似。耳鼻膜神经原纤维变性和海马皮层CA1引起的神经元死亡可能是AD记忆障碍的病理基础。

Hippocampal cortex (hippocampal formation and parahippocampal gyrus) is a key structure of the memory system and is most affected region in Alzheimer's disease (AD). To explore more fully the clinicopathological relationship between dementia symptoms such as memory disturbance and neuronal death via neurofibrillary degeneration in the hippocampal cortex in Alzheimer's disease, unaffected neurons, intracellular neurofibrillary tangles (i-NFTs) and extracellular NFTs (e-NFTs) in 22 patients with the different disease duration were morphometrically evaluated in 8 subdivisions of the hippocampal cortex, using the Gallyas hematoxylin-eosin stain. The subdivisions examined included CA1-4, prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and the entorhinal cortex (ENT). Unaffected neuron density was significantly, inversely correlated with e-NFT density and with total NFT density in all subdivisions except for PRE in AD patients. Especially in CA2, CA1, PRO and ENT, there were strong correlations between the neuron density and these NFT densities. Both unaffected neuron and e-NFT densities in CA1 and ENT were significantly correlated with the disease duration. The i/e-NFT ratio, an index of the degree and/or rate of progress of neuronal death via neurofibrillary degeneration, showed the lowest value in ENT in AD patients. The findings suggest neuronal death via neurofibrillary degeneration starts earliest and/or most rapidly progresses in ENT.Furthermore, the i/e-NFT ratios in both ENT and CA1 were significantly correlated with the disease duration, suggesting that continuous neuronal death pattern in the two subdivisions parallels disease progression in AD.Neuronal death via neurofibrillary degeneration in ENT and CA1 in the hipocampal cortex may contribute to pathological substrate of memory disturbance in AD.