Alterations of Striatal Dopamine Receptor Binding in Alzheimer Disease Are Associated With Lewy Body Pathology and Antemortem Psychosis

Abstract

Alzheimer disease with LB is associated with selective alterations in dopamine receptor density, which may contribute to the distinct clinical profile of this group. The D3 receptor may be an important target of neuroleptic treatment of psychosis in AD.

Regulation of dopamine D3 receptor in the striatal regions and substantia nigra in diffuse Lewy body disease

“…Since the expression of dopamine D 3 receptor can be induced by dopaminergic medication, such as L-dopa and dopamine agonist treatment in rodent (Bordet et al, 1997, Bordet et al, 2000) and nonhuman primate PD model (Morissette et al, 1998, Quik et al, 2000, Bezard et al, 2003); the increase of D 3 receptor density found in this study could be attributed to drug history since some patient had history of L-dopa treatment, and it is likely that other dopaminergic medication was also used in this group patient. It has been reported that AD+LB patient with psychosis (Sweet et al, 2001) had a significant higher level of D 3 receptor, so that the increase of D 3 receptor density may also be related hallucinations which was found in this group patient.…”

Regulation of dopamine D3 receptor in the striatal regions and substantia nigra in diffuse Lewy body disease

“…Since the expression of dopamine D 3 receptor can be induced by dopaminergic medication, such as L-dopa and dopamine agonist treatment in rodent (Bordet et al, 1997, Bordet et al, 2000) and nonhuman primate PD model (Morissette et al, 1998, Quik et al, 2000, Bezard et al, 2003); the increase of D 3 receptor density found in this study could be attributed to drug history since some patient had history of L-dopa treatment, and it is likely that other dopaminergic medication was also used in this group patient. It has been reported that AD+LB patient with psychosis (Sweet et al, 2001) had a significant higher level of D 3 receptor, so that the increase of D 3 receptor density may also be related hallucinations which was found in this group patient.…”

Selective loss of dopamine D2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline

“…The numbers of AD and DLB þ AD cases were small in comparison to the DLB cases and as such represent a preliminary analysis. The cortical D2 loss found in DLB was more extensive than the reduction of 17% in striatal D2 receptor density previously reported (Piggott et al, 1999), and greater than the 13% reduction of D2 binding in caudate of AD cases with coexisting Lewy body pathology (Sweet et al, 2001). There is considerable Lewy body pathology in the striatum in DLB (Duda et al, 2002;Martin-Ruiz et al, 2002), and while it may be less than in cortex, pathology in the striatum could also be related to low D2 receptor density.…”

Periodic leg movements in sleep in elderly patients with Parkinsonism and Alzheimer’s disease

“…Interestingly, although some selective monoaminergic depletion in AD has been recognized for many years (e.g., loss of D2 receptors in caudate, putamen, amygdala and hippocampus) [31–33], even in the absence of extrapyramidal signs [34], and this depletion has been implicated in behavioral syndromes in AD [35–37], our patients with AD did not demonstrate elevated rates of PLMS. It is possible that these particular patients with AD, unlike our patients with Parkinsonism, simply did not incur as widespread and pervasive as a dopaminergic deficit that predisposes for the presence of PLMS.…”

Regulation of dopamine D3 receptor in the striatal regions and substantia nigra in diffuse Lewy body disease

“…Since the expression of dopamine D 3 receptor can be induced by dopaminergic medication, such as L-dopa and dopamine agonist treatment in rodent (Bordet et al, 1997, Bordet et al, 2000) and nonhuman primate PD model (Morissette et al, 1998, Quik et al, 2000, Bezard et al, 2003); the increase of D 3 receptor density found in this study could be attributed to drug history since some patient had history of L-dopa treatment, and it is likely that other dopaminergic medication was also used in this group patient. It has been reported that AD+LB patient with psychosis (Sweet et al, 2001) had a significant higher level of D 3 receptor, so that the increase of D 3 receptor density may also be related hallucinations which was found in this group patient.…”

Selective loss of dopamine D2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline

“…The numbers of AD and DLB þ AD cases were small in comparison to the DLB cases and as such represent a preliminary analysis. The cortical D2 loss found in DLB was more extensive than the reduction of 17% in striatal D2 receptor density previously reported (Piggott et al, 1999), and greater than the 13% reduction of D2 binding in caudate of AD cases with coexisting Lewy body pathology (Sweet et al, 2001). There is considerable Lewy body pathology in the striatum in DLB (Duda et al, 2002;Martin-Ruiz et al, 2002), and while it may be less than in cortex, pathology in the striatum could also be related to low D2 receptor density.…”

Periodic leg movements in sleep in elderly patients with Parkinsonism and Alzheimer’s disease

“…Interestingly, although some selective monoaminergic depletion in AD has been recognized for many years (e.g., loss of D2 receptors in caudate, putamen, amygdala and hippocampus) [31–33], even in the absence of extrapyramidal signs [34], and this depletion has been implicated in behavioral syndromes in AD [35–37], our patients with AD did not demonstrate elevated rates of PLMS. It is possible that these particular patients with AD, unlike our patients with Parkinsonism, simply did not incur as widespread and pervasive as a dopaminergic deficit that predisposes for the presence of PLMS.…”

Regulation of dopamine D3 receptor in the striatal regions and substantia nigra in diffuse Lewy body disease

“…Since the expression of dopamine D 3 receptor can be induced by dopaminergic medication, such as L-dopa and dopamine agonist treatment in rodent (Bordet et al, 1997, Bordet et al, 2000) and nonhuman primate PD model (Morissette et al, 1998, Quik et al, 2000, Bezard et al, 2003); the increase of D 3 receptor density found in this study could be attributed to drug history since some patient had history of L-dopa treatment, and it is likely that other dopaminergic medication was also used in this group patient. It has been reported that AD+LB patient with psychosis (Sweet et al, 2001) had a significant higher level of D 3 receptor, so that the increase of D 3 receptor density may also be related hallucinations which was found in this group patient.…”

Selective loss of dopamine D2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline

“…The numbers of AD and DLB þ AD cases were small in comparison to the DLB cases and as such represent a preliminary analysis. The cortical D2 loss found in DLB was more extensive than the reduction of 17% in striatal D2 receptor density previously reported (Piggott et al, 1999), and greater than the 13% reduction of D2 binding in caudate of AD cases with coexisting Lewy body pathology (Sweet et al, 2001). There is considerable Lewy body pathology in the striatum in DLB (Duda et al, 2002;Martin-Ruiz et al, 2002), and while it may be less than in cortex, pathology in the striatum could also be related to low D2 receptor density.…”

Periodic leg movements in sleep in elderly patients with Parkinsonism and Alzheimer’s disease

“…Interestingly, although some selective monoaminergic depletion in AD has been recognized for many years (e.g., loss of D2 receptors in caudate, putamen, amygdala and hippocampus) [31–33], even in the absence of extrapyramidal signs [34], and this depletion has been implicated in behavioral syndromes in AD [35–37], our patients with AD did not demonstrate elevated rates of PLMS. It is possible that these particular patients with AD, unlike our patients with Parkinsonism, simply did not incur as widespread and pervasive as a dopaminergic deficit that predisposes for the presence of PLMS.…”