Reduction of Neuronal Intranuclear Rodlets Immunoreactive for Tubulin and Glucocorticoid Receptor in Alzheimer's Disease

Abstract

Neuronal intranuclear rodlets were described in normal brain over a century ago, but their functional significance and pathological relevance is unknown. Here, we show co‐localization of tubulin and glucocorticoid receptor‐like immunoreactivity in these intranuclear inclusions in human brain. In addition, we provide evidence for a massive reduction in their areal density in Alzheimer's disease brain, but not in another common neu rodegenerative condition, dementia with Lewy bodies. The marked reduction of these inclusions in Alzheimer's disease may support the concept of a role for stress hormones in Alzheimer's pathogenesis.

β‐Amyloid protein converting enzyme 1 and brain‐specific type II membrane protein BRI3: binding partners processed by furin

“…The concept of a role for stress hormones in Alzheimer's pathogenesis has already been suggested and recent evidence suggests that the glucocorticoid receptor plays a role in this pathology (Wetzel et al . 1995; Woulfe et al . 2002).…”

Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress

“…Ultrastructurally, they consist of parallel or more complex, cross‐hatched arrays of approximately 10‐nm longitudinal filaments. We have demonstrated that these structures are markedly reduced in the temporal cortex of patients with AD relative to age‐matched controls and those with dementia with Lewy bodies [334]. On the other hand, they are significantly increased in nigral dopaminergic neurones in the MPTP mouse model of Parkinson's disease [357].…”

The use of real-time PCR analysis in a gene expression study of Alzheimer’s disease post-mortem brains

“…In general, these housekeeping genes are expressed in all nucleated cell-types and are necessary for cell survival (Butte et al, 2001;Warrington et al, 2000). However, some of these housekeeping genes, including actins, tubulins and 18S rRNA, are regulated in AD pathogenesis (Da Silva et al, 2000;Jabbour et al, 1992;Payao et al, 1994;Vijayan et al, 2001;Woulfe et al, 2002). Thus, it is critical to determine a suitable reference gene to calculate target gene mRNA copies or fold change in the brain specimens from AD patients.…”